tag:blogger.com,1999:blog-27416724361604387082024-03-17T20:04:00.287-07:00Learning from and about cancer (chronic lymphocytic leukemia or CLL) by Dr. Brian KoffmanWhat started as a personal journey of a doctor turned patient morphed into a way to share what’s universal in dealing with cancer, in my case a nasty leukemia (CLL), a failed transplant and a successful clinical trial. The telling of my journey has become a journey to teach about CLL, related blood issues and all cancers. Please visit our new website http://cllsociety.org for the latest news and information. Smart patients get smart care™. If you want to reach me, email bkoffmanMD@gmail.comBrian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.comBlogger1077125tag:blogger.com,1999:blog-2741672436160438708.post-85831952232047594742023-08-22T00:38:00.006-07:002023-08-22T00:44:45.968-07:00 My personal decision to restart my CLL (chronic lymphocytic leukemia) treatment<div style="text-align: left;"><span style="font-family: helvetica;">I have good reasons to believe it is time to re-treat my CLL.</span></div><div style="text-align: left;"><span style="font-family: helvetica;"><br /></span></div><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">Before deciding on the best therapy choice to treat my CLL/SLL (chronic lymphocytic leukemia/small lymphocytic lymphoma), I first needed to determine if it was the right time to start therapy. <o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">In most cases, the decision about when to treat CLL is usually just that: a decision. iwCLL has clear guidelines for when treatment is indicated, which we outline in this article: <a href="https://cllsociety.org/2016/03/cll-watch-wait-start-treatment/" style="color: #954f72;">CLL: When to Watch and Wait and When to Start Treatment</a>. I think these might be more helpful in outlining when therapy is not likely appropriate because none of the iwCLL indications are met. For example, someone might have a lymphocyte count that has reached 100,000 or even 500,000 and not need any therapy if they are feeling well and have no low blood counts. <o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">On the other hand, just because one's platelets have dropped below 100,000, which is an iwCLL indication to treat, that does not mean that one urgently has to start to knock back the CLL with medication, especially if the downward trend is slow with ups and downs. One might choose to wait and follow the trend. Or not. It’s a shared medical decision.<o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">What about the opposite decision, namely starting sooner than iwCLL guidelines might suggest? <o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">That is what I am choosing.<o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">Let me start by saying this is my personal decision, relevant to my circumstances, and likely not applicable to anyone else.<o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">In brief, I was diagnosed with CLL in 2005, an aggressive variant, and within a year, I was in a world of trouble with single-digit platelets from a rare and, in my case, difficult-to-treat autoimmune complication (immune thrombocytopenic purpura or ITP) that resulted in multiple hospitalizations, an urgent splenectomy, and massive internal bleeding. ITP tried hard to kill me several times, came close, and I know how lucky I am to be alive. The ITP and the fear of it raging again drove my decision to get a first remission hematopoietic stem cell transplant (HSCT or bone marrow transplant) that quickly failed. My subsequent jump into two phase 1 clinical trials saved my life; the first was for <a href="https://cllsociety.org/2023/04/for-blood-and-money-interview/" style="color: #954f72;">PCI-32765</a>, later to become the practice-changing therapy, ibrutinib, and then for <a href="https://cllsociety.org/2018/04/day-29-the-killing-frenzy-is-done-time-to-celebrate-being-cll-free/" style="color: #954f72;">JCAR-014</a>. This CAR-T construct helps birth <a href="https://cllsociety.org/2021/04/ash-2020-dr-tanya-siddiqi-provides-an-update-on-the-transcend-cll-004-trial-lisocabtagene-maraleucel-liso-cel-in-combination-with-ibrutinib-for-patients-with-relapsed-refractory-r-r-chronic-lym/" style="color: #954f72;">list-cel</a>, a promising CAR-T cellular therapy already approved in other blood cancers but still experimental in CLL. Both gave me years of deep and wonderful remissions. My fear of recurrent ITP is my primary driver to treat it early again.<o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">After beating the odds with a 5½ year remission with CAR-T, my CLL is demanding my attention again. But not in the usual way.<o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">True, I have some <a href="https://cllsociety.org/newly-diagnosed/symptoms/" style="color: #954f72;">symptoms</a> that need attention. <o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">True, there are advantages to starting some therapies earlier when the disease burden is low. With some therapies, this can mean both higher efficacy and lower risk of adverse events when the cancer is being rapidly killed, especially early in the treatment.<o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">True, some treatment options, especially those in trials, may have narrow windows of accessibility, and when a slot is available, it may force a quicker move than planned.<o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">But the real impetus behind my decision to treat now is that I am not waiting for my blood counts to fall. I know that when my platelets fall, they fall off a cliff. In the past, my lymphocyte counts were only slightly elevated when my platelet count fell dangerously low. My other blood cell counts were all perfectly normal at the time. My ITP doesn't send a notice that it’s on its way.<o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">Today my absolute lymphocyte count is only 3.8, barely above normal, and only about ¼ of those are monoclonal chronic lymphocytic leukemia cells. That is a very low number, but I know it’s been doubling every 2-3 months for a long time with no signs of slowing down because I have been following it closely with <a href="https://cllsociety.org/treatment-and-research/mrd-and-disease-monitoring/" style="color: #954f72;">MRD</a>(measurable residual disease) testing using NGS (next-generation sequencing) specifically <a href="https://cllsociety.org/2020/08/fda-clearance-for-clonoseq-assay-to-assess-minimal-residual-disease-mrd-in-patients-with-chronic-lymphocytic-leukemia-cll/" style="color: #954f72;">Clonoseq</a> since it was barely detectable at 1/1,000,000 cells.<o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;"><span style="background: repeat white;">I am not waiting. My CLL is coming back. It’s not if I’ll need therapy; it's when. With my CLL’s return, it carries the risk of reawakening my ITP. </span><span style="background: repeat white;"><o:p></o:p></span></span></p><p class="MsoNormal" style="margin: 0in;"><span style="background: repeat white; font-family: helvetica;"><o:p> </o:p></span></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;"><span style="background: repeat white;">I am making a preemptive strike. In <i>Julius Caesar</i>, the play by Shakespeare, Brutus could have been talking about my ITP instead of his plot against Caesar “<i>Think him as<span class="apple-converted-space"> </span></i></span><i>a serpent's egg<span style="background: repeat white;">, / Which, hatched, would as his kind, grow mischievous, / And kill him in the shell</span></i><span style="background: repeat white;">." </span><span style="background: repeat white;"><o:p></o:p></span></span></p><p class="MsoNormal" style="margin: 0in;"><span style="background: repeat white; font-family: helvetica;"><o:p> </o:p></span></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">I won't let my ITP hatch. I am treating early.<o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">Your decision is likely to be different. Waiting and postponing therapy is often the very best option. Everyone's case is unique. The only universal is that nearly always the timing of when to start treatment for chronic lymphocytic leukemia should be a carefully considered shared medical decision between the patient and the healthcare provider.<o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">Stay strong; we are all in this together.<o:p></o:p></span></p><p class="MsoNormal" style="margin: 0in;"><o:p><span style="font-family: helvetica;"> </span></o:p></p><p class="MsoNormal" style="margin: 0in;"><span style="font-family: helvetica;">Brian Koffman MDCM (retired) MS Ed</span></p><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-71793839246109908492023-07-21T01:06:00.002-07:002023-07-21T01:08:03.076-07:00 ASH 2022: Adverse Events from BTK Inhibitors in Clinical Trials<p><b style="font-family: Calibri, sans-serif;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Bottom Line:</span></b></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">This meta-analysis or combination of 61 trials demonstrated that atrial fibrillation, hypertension, and diarrhea were more common with ibrutinib, and some bleeding and infection events were more common with acalabrutinib and zanubrutinib.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Who Performed the Research and Where Was it Presented:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">A consortium of doctors led by Dr. Jacqueline Wang of NYU Langone Health presented the abstract at ASH 2022.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Background:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">We are aware of how Bruton’s tyrosine kinase inhibitors (BTKi’s) have revolutionized the therapeutic landscape of B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic leukemia (CLL / SLL), mantle cell lymphoma (MCL), and Waldenstrom’s macroglobulinemia (WM). Ibrutinib was the first FDA-approved BTKi. Unfortunately, its off-target effects have resulted in several adverse events (AEs) of concern, such as atrial fibrillation (an irregular heart rhythm), hypertension, hemorrhage, and diarrhea. Acalabrutinib and zanubrutinib are second-generation, more selective BTKIs developed to minimize off-target effects. While multiple trials have been conducted for these BTKi’s in B-cell malignancies, direct comparison of toxicity profiles between BTKi’s has been limited to just three trials. The purpose of this study was to augment our understanding of these side effects reported with the three approved BTKIs by compiling together many clinical trials.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Methods:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">PubMed and major hematology/oncology conference abstracts such as ASH or EHA, or ASCO were searched (last updated query on July 11, 2022) for trials of ibrutinib, acalabrutinib, and zanubrutinib in B-cell malignancies. In addition, adverse events (AEs) of clinical interest or AEs reported by ≥10% of the included trials were analyzed.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Results:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><ul style="margin-bottom: 0in; margin-top: 0in;" type="disc"><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">A total of 61 trials were included involving 6458 patients and 68 treatment arms: ibrutinib (n=30; 44%), ibrutinib plus CD20-mAb (n=14; 21%), acalabrutinib (n=11; 16%), acalabrutinib plus CD20-monoclonal antibodies (mAb) such as rituximab (n=2; 3%), zanubrutinib (n=10; 15%), and zanubrutinib plus CD20-mAb (n=1; 1%).<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">More than half of the trials were in CLL / SLL (n=32), the rest in MCL (n=10) or WM (n=9);<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">38 trials were relapsed/refractory setting and 14 in frontline.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">Only three trials involved a randomized comparison between different BTKis (ASPEN, ELEVATE-RR, and ALPINE).<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">A total of 65 different AEs were analyzed.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">The most common all-grade AEs across all drugs and trials were infection (62.2%), hemorrhage (41.5%), diarrhea (34.3%), fatigue (22.8%), neutropenia or low neutrophil count (21.6%), and upper respiratory infection (URI) (21.0%).<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">The most common grade ≥3 or more serious AEs included neutropenia or low neutrophil count (14.9%) and infection (12.3%).<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">All grade/grade ≥3 atrial fibrillation incidences were 6.0%/2.5%, respectively, and for hypertension were 12.5%/7.8%, respectively.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">Comparisons between AEs in trials resulting from ibrutinib and AEs in either acalabrutinib or zanubrutinib were made.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">AEs of any grade that occurred more frequently with ibrutinib included atrial fibrillation (acalabrutinib/zanubrutinib vs. ibrutinib odds ratio or OR 0.30), hypertension (OR 0.47), anemia (OR 0.67), low platelets or thrombocytopenia (OR 0.57), nausea (OR 0.67), vomiting (OR 0.77), and diarrhea (OR 0.49).<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">Grade ≥3 or more severe AEs that occurred more frequently with ibrutinib included atrial fibrillation (OR 0.29), hypertension (OR 0.37), diarrhea (OR 0.52), and rash (OR 0.30).<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">All grade AEs that occurred more frequently with acalabrutinib/zanubrutinib included contusions (OR 1.50), hematuria (blood in the urine) (OR 1.96), leukopenia (low white blood cell count (OR 2.93), second primary malignancies (OR 1.53), upper respiratory infections such as the common cold (OR 1.29), and headaches (OR 2.03). The risk of headaches when starting acalabrutinib is well known.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo2; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">Grade ≥3 AEs that occurred more frequently with acalabrutinib/zanubrutinib included leukopenia (low white blood cell counts) (OR 2.08), upper respiratory infections (OR 1.74), and pneumonia (OR 1.35).<o:p></o:p></span></li></ul><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Conclusions:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">This is the largest meta-analysis of AEs reported with covalent BTKIs. The results help us better understand the side effects of BTKIs in CLL and other related B-cell lymphomas and cancers. Atrial fibrillation, hypertension, and diarrhea were more common with ibrutinib, similar to what was seen in the head-to-head randomized trials. Additionally, bleeding and infection were more common with acalabrutinib/zanubrutinib. This needs further study to determine whether it is a valid finding.</span></p><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Links and Resources:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Watch my review of this abstract:</span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"></span></p><div class="separator" style="clear: both; text-align: center;"><iframe allowfullscreen="" class="BLOG_video_class" height="266" src="https://www.youtube.com/embed/bzf_qJ1Ted8" width="320" youtube-src-id="bzf_qJ1Ted8"></iframe></div><br />ASH 2022: Dr. Brian Koffman on Adverse Events From BTKi’s in Clinical Trials for B-Cell Malignancies<o:p></o:p><p></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">The actual trial abstract is:<a href="https://ashpublications.org/blood/article/140/Supplement%201/9882/492841/Comparison-of-Treatment-Emergent-Adverse-Events-of"><b> </b><b><span style="color: blue; text-decoration: none;">Comparison of Treatment-Emergent Adverse Events of Covalent BTK Inhibitors in Clinical Trials in B-Cell Malignancies: A Systematic Review and Meta-Analysis.</span></b></a><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Stay strong. We are all in this together.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Brian<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Brian Koffman MDCM (retired) MS Ed (he, him, his)<br />Co-Founder, Executive VP, and Chief Medical Officer<br />CLL Society, Inc.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><style class="WebKit-mso-list-quirks-style">
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</style><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-18170833188717055302023-07-21T00:57:00.002-07:002023-07-21T00:58:49.904-07:00 Dr. Stephan Stilgenbauer on the Evolution of CLL to Richter’s Syndrome from ASH 2022<p><i style="font-family: Calibri, sans-serif;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Medically reviewed and interview by </span></i><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><a href="https://cllsociety.org/about-us/dr-brian-koffman/" target="_blank"><i><span style="color: blue; text-decoration: none;">Dr. Brian Koffman</span></i></a>.</span></p><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">The Bottom Line:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">This new research identifies some of the genetic changes that drive the evolution of CLL to Richter’s syndrome. Researchers hope this information can be used to develop better treatments for Richter’s syndrome.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Who Performed the Research and Where Was it Presented:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Dr. Stephen Stilgenbauer from Ulm University and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2022.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Background:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><a href="https://cllsociety.org/treatment-and-research/richters-transformation/" target="_blank"><span style="color: blue;">Richter’s syndrome</span></a> (a.k.a. Richter’s transformation) is a rare complication of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), where the cancer cells transform into a much more aggressive lymphoma. It currently has no approved therapies and is associated with an extremely poor prognosis. One way of identifying potential therapeutic targets is to study the biology and mechanisms contributing to the development of Richter’s syndrome. The hope is that it would help scientists to identify better approaches for treating Richter’s syndrome.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Dr. Brian Koffman interviewed <a href="https://www.uni-ulm.de/fileadmin/website_uni_ulm/sfb1074/B1/CV_Stilgenbauer.pdf" target="_blank"><span style="color: blue;">Dr. Stephan Stilgenbauer</span></a>, Professor of Medicine and Medical Director of the Comprehensive Cancer Center at Ulm University in Germany. They discussed new research looking at the genetic changes that drive the evolution of CLL into Richter’s syndrome. Much of this is very technical information that will help inform new therapies.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Methods and Participants:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Researchers analyzed all the DNA in matched Richter’s syndrome and CLL samples from 52 patients. They also analyzed DNA on a validation cohort of 43 independent Richter’s syndrome cases. They used this information to trace the evolution of CLL to Richter’s syndrome.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Results:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><ul style="margin-bottom: 0in; margin-top: 0in;" type="disc"><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">Researchers identified several genes that they think are drivers of Richter’s syndrome (including IRF2BP2, SRSF1, B2M, DNMT3A, CCND3) and other alterations in patients’ genomes.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">Some alterations in key signaling pathways are pre-existing in CLL, such as changes in DNA damage response, NOTCH signaling, and MAPK signaling.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">However, changes in other signaling pathways appear to newly occur with the transformation to Richter’s syndrome, such as changes in inflammatory signaling, cell cycle regulation, immune evasion, and MYC signaling.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">Increasing massive chromosomal rearrangement (chromothripsis) was identified as one of the hallmarks of Richter’s syndrome.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">Richter’s syndrome is genetically distinct from diffuse large B cell lymphoma (DLBCL).<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span face="Arial, sans-serif" style="font-size: 13.5pt;">Though none of the pathways identified in this research have drugs available in the clinic yet, researchers are hopeful that this new information will help to drive the development of new solutions for Richter’s syndrome.<o:p></o:p></span></li></ul><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Conclusions:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">This new research identifies some of the genetic changes that drive the evolution of CLL to Richter’s syndrome. Researchers hope this information can be used to develop better treatments for Richter’s syndrome.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Links and Resources:</span></b><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Watch the interview on the abstract here:<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"></p><div class="separator" style="clear: both; text-align: center;"><iframe allowfullscreen="" class="BLOG_video_class" height="266" src="https://www.youtube.com/embed/xb7qrXEpo7U" width="320" youtube-src-id="xb7qrXEpo7U"></iframe></div><p></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">ASH 2022: Dr. Stephan Stilgenbauer on the Evolution of CLL to Richter Syndrome</span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;">Here is the actual ASH abstract: <a href="https://ashpublications.org/blood/article/140/Supplement%201/1530/490658/Evolutionary-History-of-Transformation-from?searchresult=1" target="_blank"><span style="color: blue;">Evolutionary History of Transformation from Chronic Lymphocytic Leukemia to Richter Syndrome</span></a><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="color: #0c0c0c; font-size: 13.5pt;">Ann Liu PhD</span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="color: #0c0c0c; font-size: 13.5pt;"> </span></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><style class="WebKit-mso-list-quirks-style">
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</style><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-52037335846834352232022-08-12T01:58:00.003-07:002022-08-12T02:09:41.430-07:00ASH 2021: Dr. Jeff Sharman on Zanubrutinib for BTK Inhibitor-Intolerant Patients with Chronic Lymphocytic Leukemia (CLL)<p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; margin: 0in; orphans: auto; text-align: start; text-indent: 0px; widows: auto;"><span style="font-family: arial;"><span style="color: #0c0c0c;"><span style="color: black; font-size: medium;"><span style="caret-color: rgb(0, 0, 0);">At the American Society of Hematology (ASH) 2021 </span></span><span style="font-size: medium;"><span style="caret-color: rgb(0, 0, 0);">Annual Conference and </span></span><span style="font-size: medium;"><span style="caret-color: rgb(0, 0, 0);">Exhibition</span><span style="color: black;"><span style="caret-color: rgb(0, 0, 0);">, I interviewed </span></span></span></span><a href="https://www.oregoncancer.com/physicians/jeff-sharman-md" style="caret-color: rgb(0, 0, 0); color: black; font-size: 18px; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; text-decoration: none; text-transform: none; white-space: normal; word-spacing: 0px;" target="_blank"><span style="color: blue;">Dr. Jeff Sharman</span></a><span style="caret-color: rgb(0, 0, 0); color: #0c0c0c; font-size: 18px; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; text-decoration: none; text-transform: none; white-space: normal; word-spacing: 0px;">, a hematologist/oncologist at Willamette Valley Cancer Institute in Eugene, OR. We discussed zanubrutinib and its use in patients who could not tolerate previous BTK inhibitors.</span></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;"><br /></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; margin: 0in; orphans: auto; text-align: start; text-indent: 0px; widows: auto;"><span style="font-family: arial;"><span style="color: #0c0c0c;"><span style="color: black; font-size: medium;"><span style="caret-color: rgb(0, 0, 0);">Chemotherapy was </span></span><span style="font-size: medium;"><span style="caret-color: rgb(0, 0, 0);">until</span></span><span style="color: black; font-size: medium;"><span style="caret-color: rgb(0, 0, 0);"> recently the only treatment available to CLL/SLL patients until the BTK inhibitor ibrutinib revolutionized the treatment of CLL/SLL.</span></span></span><span face="-webkit-standard, serif" style="caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; text-decoration: none; text-transform: none; white-space: normal; word-spacing: 0px;"><o:p></o:p></span></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;"><br /></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;">Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib are very effective for treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).But, they are meant to be taken continuously, and some patients can have trouble tolerating their side effects. Therefore, second-generation BTK inhibitors such as acalabrutinib and zanubrutinib have been designed with the goal of reducing side effects.</span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;"><br /></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;">Takeaways:<o:p></o:p></span></p><ul style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin-bottom: 0in; margin-top: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;" type="disc"><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span style="font-family: arial; font-size: 13.5pt;">BTK inhibitors are wonderfully effective, but the problem is that they do have side effects.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span style="font-family: arial; font-size: 13.5pt;">Even small to moderate side effects can be discouraging for patients when you have to take a drug indefinitely.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span style="font-family: arial; font-size: 13.5pt;">Some side effects patients may experience with ibrutinib include joint pain, muscle cramps, bruising, high blood pressure, and an irregular heartbeat (atrial fibrillation).<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span style="font-family: arial; font-size: 13.5pt;">Second-generation BTK inhibitors such as acalabrutinib and zanubrutinib were designed to be more specific and minimize side effects.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span style="font-family: arial; font-size: 13.5pt;">In head-to-head studies, patients taking acalabrutinib or zanubrutinib have lower rates of high blood pressure and atrial fibrillation than those taking ibrutinib. <o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span style="font-family: arial; font-size: 13.5pt;">For this phase 2 study, 64 patients who could not tolerate ibrutinib or acalabrutinib due to side effects were switched to zanubrutinib.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span style="font-family: arial; font-size: 13.5pt;">When patients switched to zanubrutinib, the symptom which previously caused them to stop taking their last BTK inhibitor did not recur in 73% of patients. If a symptom did recur, it tended to recur at a lower intensity.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span style="font-family: arial; font-size: 13.5pt;">When patients switched to zanubrutinib, they experienced fewer side effects or were better able to tolerate those side effects.<o:p></o:p></span></li><li class="MsoNormal" style="color: #0c0c0c; mso-list: l0 level1 lfo1; tab-stops: list .5in; vertical-align: baseline;"><span style="font-family: arial; font-size: 13.5pt;">Additionally, patients demonstrated they maintained (41%) and improved (53%) responses with zanubrutinib treatment.<o:p></o:p></span></li></ul><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;"><br /></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;">Conclusions:<o:p></o:p></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;"><br /></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;">Zanubrutinib is not yet approved for CLL, but can be used "off-label" to treat CLL/SLL.</span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;"><br /></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;">Second-generation BTK inhibitors appear to be just as effective as ibrutinib but with fewer side effects making them possibly more tolerable for long term use.<o:p></o:p></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;"><br /></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;">Please enjoy my <a href="https://www.youtube.com/watch?v=0aFn-NEzO2s">video interview with Dr. Sharman</a> from the ASH meeting, held in December 2021 in Atlanta, GA, and virtually.</span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="font-family: arial;"><br /></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;">You can read the actual abstract here: <a href="https://ashpublications.org/blood/article/138/Supplement%201/1410/480321/Phase-2-Study-of-Zanubrutinib-in-BTK-Inhibitor" target="_blank"><span style="color: blue;">Phase 2 Study of Zanubrutinib in BTK =Inhibitor-Intolerant Patients (Pts) with Relapsed/Refractory B-Cell Malignancies</span></a><o:p></o:p></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;">Take care of yourself first.<o:p></o:p></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;"><br /></span></p><p class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; margin: 0in; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;"><span style="color: #0c0c0c; font-family: arial; font-size: 13.5pt;">Thanks to Ann Liu for the notes on my ASH interview.</span></p><style class="WebKit-mso-list-quirks-style">
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</style><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-29554030552585560702021-08-13T22:31:00.003-07:002021-08-14T12:54:03.268-07:00ASH 2020: Dr. Anthony Mato on LOXO-305 A Next Generation Highly Selective Non-Covalent BTK inhibitor.<p><span style="font-family: arial;"><span face="Roboto, Helvetica, Arial, Verdana, sans-serif" style="font-size: 14px;">In an oral presentation during ASH 2020, Dr. Anthony Mato discussed LOXO-305, a new generation BTKi (Bruton Tyrosine Kinase Inhibitor) that blocks a key step in the B cell receptor (BCR) pathway. In doing so, it blocks pro-survival and “homing” messages to the CLL cells, forcing the cancer cells to leave their protective niches in the lymph nodes and bone marrow, and float out into the blood stream, eventually dying.</span></span></p><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;">Ibrutinib was the first approved BTKi and it revolutionized the treatment of CLL because of its ability to provide a durable response in most patients, including those with high-risk features such as del 17p or TP53.</span></p><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;">However, especially in the relapsed and refractory setting, some CLL cells may eventually be able to escape inhibition from ibrutinib and other similar BTKis such as acalabrutinib and zanabrutinib (not approved for CLL at the time of this writing). The most common way this happens is by a mutation in the drug’s binding site at C481 preventing tho<span style="margin: 0px; padding: 0px; text-decoration: line-through;">se</span> 1<span style="font-size: 10.588234901428223px; line-height: 0; margin: 0px; padding: 0px; position: relative; top: -0.5em; vertical-align: baseline;">st</span> generation BTKis from irreversibly binding to and blocking BTK, rendering those drugs largely ineffective.</span></p><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;">LOXO-305 binds “reversibly” and does not seem to be affected by changes in the C481 binding site. It remains able to turn off BTK when the irreversible binders are no longer effective.</span></p><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;">Dr. Mato discusses the CLL data from the BRUIN trial, which is the first in-human trial of LOXO-305 for CLL and NHL (Non-Hodgkin Lymphomas)</span></p><ul style="font-size: 14px; line-height: 19.60000228881836px; list-style-image: initial; list-style-position: initial; margin: 0px 0px 20px 20px; padding: 0px;"><li style="margin: 0px; padding: 0px;"><span style="font-family: arial;">170 CLL patients were studied.</span><ul style="line-height: 19.60000228881836px; list-style: disc; margin: 0px 0px 0px 20px; padding: 0px;"><li style="margin: 0px; padding: 0px;"><span style="font-family: arial;">80% had received ibrutinib or acalabrutinib.</span></li></ul></li><li style="margin: 0px; padding: 0px;"><span style="font-family: arial;">200 mg is the daily dose.</span></li><li style="margin: 0px; padding: 0px;"><span style="font-family: arial;">Fatigue, diarrhea, and bruising were the only side effects above 10%.</span></li><li style="margin: 0px; padding: 0px;"><span style="font-family: arial;">< 1% had atrial fibrillation.</span></li><li style="margin: 0px; padding: 0px;"><span style="font-family: arial;">Response rate for all 63%. If one looked at just the patients who were assessed at > 6 months or greater giving the medicine some time to work, the response rate went up to 86%.</span></li><li style="margin: 0px; padding: 0px;"><span style="font-family: arial;">94% of those who responded are still on drug.</span></li><li style="margin: 0px; padding: 0px;"><span style="font-family: arial;">Patients responded well even they failed multiple other drugs and were running out of options.</span></li><li style="margin: 0px; padding: 0px;"><span style="font-family: arial;">First study of one BTK inhibitor after failing another BKI inhibitor.</span></li></ul><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;">Conclusions:</span></p><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;">Blocking the BTK pathway works amazing well for CLL patients, so when patients relapse on a first generation BTK inhibitor, there is good sense in trying another drug that uses a different mechanism to block the B cell receptors through BTK inhibition. Early data from the BRUIN trial suggest that LOXO-305 seems is a promising new option with regard to efficacy and tolerability and deserves further study to assess it in larger numbers of patients.</span></p><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;">Here is a link to the actual trial on Clinicaltrials.gov that Dr. Mato describes in our ASH interview: <a href="https://clinicaltrials.gov/ct2/show/NCT03740529?term=Loxo+305&cond=CLL&draw=2&rank=2" style="color: #52adad; margin: 0px; padding: 0px;">A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL</a>.</span></p><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;">Please enjoy our interview:</span></p><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;"><iframe allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen="" frameborder="0" height="900" src="https://www.youtube.com/embed/HDGJ4nDrwOE?feature=oembed" style="margin: 0px; max-width: 100%; padding: 0px;" title="ASH 2020 Dr. Anthony Mato #1 LOXO-305 A Next Generation Highly Selective Non-Covalent BTK inhibitor" width="1200"></iframe></span></p><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;">Here is the ASH abstract: <a href="https://ash.confex.com/ash/2020/webprogram/Paper134970.html" style="color: #52adad; margin: 0px; padding: 0px;">LOXO-305, A Next Generation, Highly Selective, Non-Covalent BTK Inhibitor in Previously Treated CLL/SLL: Results from the Phase 1/2 BRUIN Study</a>.</span></p><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;">Stay strong. We are all in this together.</span></p><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;">Brian</span></p><p style="font-size: 14px; line-height: 19.60000228881836px; margin: 0px 0px 20px; padding: 0px;"><span style="font-family: arial;">Brian Koffman MDCM (retired) MS Ed</span></p><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-57842504333750154522021-08-12T01:54:00.000-07:002021-08-12T01:54:05.247-07:00 ASH 2020: Dr. Arnon Nagler on Safety and Efficacy of CD19-CAR T Cells in Richter’s Transformation After Targeted Therapy for Chronic Lymphocytic Leukemia (CLL)<p><span style="font-family: "Times New Roman", serif;">At the virtual ASH 2020 Annual Conference and Exposition,</span><span style="font-family: "Times New Roman", serif;"> </span><a href="https://schedule.swedish.org/directory/hematology/1221-madison-street-159507-1383555" style="font-family: "Times New Roman", serif;">Dr. John Pagel of Swedish Hospital</a><span style="font-family: "Times New Roman", serif;"> </span><span style="font-family: "Times New Roman", serif;">and one of CLL Society’s directors interviewed</span><span style="font-family: "Times New Roman", serif;"> </span><a href="https://www.shebaonline.org/doctors/dr-arnon-nagler/" style="font-family: "Times New Roman", serif;">Dr. Arnon Nagler</a><span style="font-family: "Times New Roman", serif;"> of Sheba Medical Center in Israel concerning using “in-house” CAR-T cells made locally at his medical center for Richter’s Transformation patients.</span></p><p class="MsoNormal" style="font-size: medium;"><o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;"><a href="https://cllsociety.org/2017/04/richter-transformation/">Richter’s Transformation (RT)</a> is usually an aggressive transformation of chronic lymphocytic leukemia into a fast-moving lymphoma, usually clonally related, DLBCL (diffuse large B-cell lymphoma). RT is associated with a very poor response to most therapies and has a discouraging prognosis.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">It remains one of the most pressing unmet needs in CLL patients.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">That is why when the Israeli group showed that six of nine Richter’s patients responded to CAR-T therapy, their research was recognized for its importance and given a slot as one of the six oral CLL clinical presentations at ASH 2020.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">Take Aways:<o:p></o:p></p><p class="MsoListParagraphCxSpFirst" style="mso-list: l2 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->These were mostly heavily pretreated patients, all having progressed on ibrutinib and/or venetoclax<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l2 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->Del 17p/TP53 was found in 83% (five out of six) of those tested<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l2 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->Despite these poor markers and their aggressive disease, six of nine patients had complete remissions<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l2 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->Only two of these six progressed within a year, including one who went on to have a bone marrow transplant<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l2 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->One significant advantage of an “in-house” CAR-T is that the waiting time to manufacture the CAR-T is only ten days, so “bridging therapy” to keep the fast-moving Richter’s under control while waiting for the cells is less likely to be needed<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo2; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->No new problems or adverse events were noted in this Richter’s population. Just the usual three that are seen in most CAR-T treatments:<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="margin-left: 1.0in; mso-add-space: auto; mso-list: l1 level2 lfo3; text-indent: -.25in;"><!--[if !supportLists]-->1.<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span><!--[endif]-->Cytokine release syndrome (CRS): An acute systemic inflammatory syndrome characterized by fever, flu-like symptoms, and has the potential for low blood pressure and multiple organ dysfunction. It is usually of short duration, is now well understood, and can be safely managed in nearly all cases.<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="margin-left: 1.0in; mso-add-space: auto; mso-list: l1 level2 lfo3; text-indent: -.25in;"><!--[if !supportLists]-->2.<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span><!--[endif]-->Neurotoxicity: Might include headache, confusion, delirium, language disturbance, coma, seizures, and rarely acute brain swelling. It is usually mild and is almost always fully reversible.<o:p></o:p></p><p class="MsoListParagraphCxSpLast" style="margin-left: 1.0in; mso-add-space: auto; mso-list: l1 level2 lfo3; text-indent: -.25in;"><!--[if !supportLists]-->3.<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span><!--[endif]-->Low blood counts: May include anemia, low neutrophils, low platelets, and low lymphocytes. It can be persistent, but counts do recover over time.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">Conclusions:<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">These results give us clear proof that CAR-T cellular therapy can work in Richter’s Transformation, and that is much-needed good news. The numbers are small, so larger studies will be needed, and I am sure will be done to confirm the promising findings.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">But there remain many unanswered questions.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">Can CAR-T be curative for some? For at least some patients, there is reason to be hopeful this might be the case.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">Should it be used as a bridge to an allogeneic stem cell (bone marrow) transplant for RT patients to “consolidate” their response? We know the transplants (while high-risk and not perfect) still offer the best, most durable responses in Richter’s to those who are well enough to undergo the procedure.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">Here is Dr. Pagel’s interview with Professor Nagler from ASH 2020: <a href="https://youtu.be/yFOWNR0x-u0"><span style="font-family: Arial, sans-serif; font-size: 11.5pt;">https://youtu.be/yFOWNR0x-u0</span></a><o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><u><span style="color: blue; font-family: Arial, sans-serif; font-size: 11.5pt;"> </span></u></p><p class="MsoNormal" style="font-size: medium;">A transcript of the interview is being provided, as some of the interview is difficult to understand. We ask you to rely on the abstract linked below for study details, as we are not certain of the accuracy of every word in the transcript.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">Here is the ASH abstract: <a href="https://ash.confex.com/ash/2020/webprogram/Paper138904.html">Safety and Efficacy of CD19-CAR T Cells in Richter’s Transformation after Targeted Therapy for Chronic Lymphocytic Leukemia</a><o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><style class="WebKit-mso-list-quirks-style">
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</style><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-89038959283346241492021-08-12T01:49:00.002-07:002021-08-12T01:49:24.153-07:00EHA 2021: Dr. Anthony Mato on pirtobrutinib (LOXO-305) for Richter’s transformation in chronic lymphocytic leukemia (CLL) <p><span style="font-family: Calibri, sans-serif;">Richter’s transformation (a.k.a. Richter’s syndrome) is a rare complication of chronic lymphocytic leukemia (CLL) where the cancer cells transform into a much more aggressive lymphoma. It occurs in 2-10% of CLL patients, and it is associated with very rapid disease progression, limited therapeutic options, and poor survival. Outcomes have generally been poor because the lymphoma does not respond well to traditional treatments. While chemotherapy is often used to treat Richter’s transformation, it is not very effective. </span></p><p class="MsoNormal" style="font-size: medium;"><o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">At the annual meeting of the European Hematology Association (EHA) 2021,I interviewed <a href="https://www.mskcc.org/cancer-care/doctors/anthony-mato">Dr. Anthony Mato</a>, Director of the CLL Program at Memorial Sloan Kettering Cancer Center. They discussed preliminary results from a clinical trial of pirtobrutinib (formerly LOXO-305) in a subset of patients with Richter’s transformation.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"> <o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><b>Takeaways:<o:p></o:p></b></p><p class="MsoListParagraphCxSpFirst" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->This is a phase 1/2 clinical trial of pirtobrutinib, which is a highly-selective, reversible (non-covalent) Bruton’s tyrosine kinase (BTK) inhibitor we have previously discussed <a href="https://cllsociety.org/2021/01/ash-2020-dr-anthony-mato-on-loxo-305-a-next-generation-highly-selective-non-covalent-btk-inhibitor/">here</a>.<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->The trial is currently ongoing, and this portion of the trial is enrolling patients with previously treated Richter’s syndrome.<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->Thus far, 17 patients with Richter’s transformation have been enrolled in the trial. <o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->These patients have already been heavily treated. The median number of prior therapies for CLL was 6, and the median number of prior therapies specifically for Richter’s transformation was 2.<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->Thus far, 15 patients have had a response assessment, and 67% (2 out of 3) responded to treatment.<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->Though it is still early on, some patients have continued to respond after 6+ months of follow-up.<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->Pirtobrutinib is probably not a cure for Richter’s transformation, but it may help stabilize the disease, improve quality of life, and potentially serve as a bridge to other therapies such as CAR-T therapy or stem cell transplant.<o:p></o:p></p><p class="MsoListParagraphCxSpLast" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->Thus far, pirtobrutinib has been well-tolerated with very few serious adverse events.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><b> </b></p><p class="MsoNormal" style="font-size: medium;"><b>Conclusions:<o:p></o:p></b></p><p class="MsoNormal" style="font-size: medium;">There is a large unmet need for effective treatments for Richter’s transformation. Even though these results are only in a small number of patients with a short follow-up period, pirtobrutinib seems like a promising candidate thus far. This is encouraging news for patients who have few options, and we hope that we continue to see positive results with longer term follow up in more patients. If you are interested in participating, the trial is still ongoing at multiple sites in the United States and worldwide. More information can be found <a href="https://clinicaltrials.gov/ct2/show/NCT03740529">here</a>.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">Please enjoy this brief interview with Dr. Mato from the virtual EHA meeting which was held June 2021.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: yellow;"><Video link> </span><a href="https://youtu.be/OOV7myAT4aA" target="_blank"><span style="background-color: yellow;">https://youtu.be/OOV7myAT4aA </span></a><o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">You can read the actual abstract here: <a href="https://library.ehaweb.org/eha/2021/eha2021-virtual-congress/325284/anthony.r.mato.pirtobrutinib.28loxo-30529.a.next.generation.highly.selective.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dpirtobrutinib">Pirtobrutinib (LOXO-305), a next generation, highly-selective, non-covalent BTK inhibitor in previously treated Richter transformation: results from the phase 1/2 BRUIN study</a><o:p></o:p></p><style class="WebKit-mso-list-quirks-style">
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</style><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-38609685200185361912021-08-12T01:46:00.003-07:002021-08-12T01:46:59.905-07:00ASH 2020: Dr. Peter Hillmen on the CLARITY Trial of Ibrutinib Plus Venetoclax for Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) <p> </p><style class="WebKit-mso-list-quirks-style">
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</style><br /><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib and BCL2 inhibitor venetoclax have been very successful as individual therapies for treating chronic lymphocytic leukemia (CLL), but on their own they rarely lead to the eradication of measurable (a.k.a. minimal) residual disease (MRD). Researchers have been very interested in whether they can combine these therapies to improve outcomes for patients and achieve better remissions. They also want to determine how long would patients need to take the combination for to achieve deep remissions.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">At the annual meeting of the American Society of Hematology (ASH) 2020, Dr. John Pagel of the CLL Society Board of Directors interviewed <a href="https://www.nuffieldhealth.com/consultants/professor-peter-hillmen">Dr. Peter Hillmen</a>, Professor of Experimental Hematology at the University of Leeds in the United Kingdom. They discussed updates to the phase II CLARITY trial which has been evaluating the efficacy of combination ibrutinib + venetoclax in patients with relapsed/refractory CLL.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"> <o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><b>Takeaways:<o:p></o:p></b></p><p class="MsoListParagraphCxSpFirst" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->The CLARITY trial is a phase II study testing the combination of ibrutinib + venetoclax in patients with relapsed/refractory CLL. The primary endpoint the researchers were evaluating was undetectable measurable residual disease (uMRD) after one year, and those results have been published <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879312/">here</a>.<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->Almost all patients (89%) responded to treatment.<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->Responses continued to improve after the first year of combination treatment with 24/50 (48%) patients achieving uMRD in the bone marrow at month 26 compared to 20/50 (40%) at month 14.<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->After 3 years, responses to ibrutinib + venetoclax were sustained even though many patients had discontinued treatment due to achieving uMRD.<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->Patients who had not yet achieved uMRD by year 2 were allowed to extend combination treatment duration for and additional year.<o:p></o:p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->While there was some benefit in year 3, most of the benefit occurs earlier on. This suggests that patients who respond probably only need a limited duration of therapy, and more is not necessarily better.<o:p></o:p></p><p class="MsoListParagraphCxSpLast" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]-->The response to treatment in the first 2-3 months seems to predict who will achieve uMRD. Thus, clinicians might want to alter the treatment plan if a patient doesn’t respond to ibrutinib + venetoclax early on.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><b> </b></p><p class="MsoNormal" style="font-size: medium;"><b>Conclusions:<o:p></o:p></b></p><p class="MsoNormal" style="font-size: medium;">These results show that combination therapy with ibrutinib + venetoclax can produce deep remissions with eradication of MRD in many but not all patients with difficult to treat relapsed/refractory CLL. Thus far, these responses seem to be sustained even with planned treatment discontinuation once uMRD is achieved, and researchers continue to follow these patients.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">The logical extension of this research is to see if ibrutinib + venetoclax can be used as a first line treatment. We know that the best responses are with first line treatment, and some phase II trials of ibrutinib + venetoclax as a first line treatment for CLL have shown <a href="https://cllsociety.org/2020/07/ash-2019-dr-nitin-jain-on-the-combination-of-ibrutinib-and-venetoclax-for-chronic-lymphocytic-leukemia-cll/">promising results</a>. However, phase II trials usually do not have a comparator group so the results can’t be directly compared to other treatments. To address this gap in knowledge, a large clinical trial is currently underway to test ibrutinib + venetoclax as a first line therapy vs. ibrutinib alone or FCR chemoimmunotherapy.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">Please enjoy this brief interview with Dr. Hillmen from the virtual ASH meeting which was held December 2020.<o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: yellow;"><Video link> </span><a href="https://youtu.be/05oooiOKGDw" target="_blank"><span style="background-color: yellow;">https://youtu.be/05oooiOKGDw </span></a><o:p></o:p></p><p class="MsoNormal" style="font-size: medium;"><o:p> </o:p></p><p class="MsoNormal" style="font-size: medium;">You can read the actual abstract here: <a href="https://ashpublications.org/blood/article/136/Supplement%201/17/469948/Continued-Long-Term-Responses-to-Ibrutinib?searchresult=1">Continued Long Term Responses to Ibrutinib + Venetoclax Treatment for Relapsed/Refractory CLL in the Blood Cancer UK TAP Clarity Trial</a><o:p></o:p></p><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-3723415130037562162021-04-08T12:00:00.000-07:002021-04-08T12:00:05.894-07:00Dr. John Byrd’s Exciting Move to the University of Cincinnati: The significance for me and other CLL (chronic lymphocytic leukemia) patients<p><span style="font-family: Arial, sans-serif; font-size: 11pt;">I have known Dr. John Byrd since we met at ASH in 2011 and he has been my chronic lymphocytic leukemia (CLL) doctor most of that time.</span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">It would not be a stretch to say that his care in a Phase I/II trial of PCI-32765 (ibrutinib) at Ohio State University in Columbus saved my life.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">It would also not be fair if it weren’t mentioned that I have been blessed with excellent care from several other doctors. These have included superstar Dr. Tom Kipps, Drs. Sanjay Sharma (hematology), David Rhodes (family medicine), many local healthcare providers, and a recent addition to my team, CLL expert Dr. Alexey Danilov. There have been many others across the US and from around the world who have generously nudged me or shared breaking news pertinent to my circumstances, even when I was not their patient or had only seen them once many years ago. These consultations have been led by Dr. Furman and have included Drs. Kanti Rai, John Pagel, Adrian Weistner, Michael Hallek, Stephen Forman, and Neil Kay.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">While I have been lucky to know so many world-class CLL doctors, for the last 10 years, Dr. Byrd has been my go-to clinician and the final arbitrator of many split decisions in my treatment journey. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">We have become good friends over the past decade, which has been eventful and revolutionary for chronic lymphocytic leukemia patients. Today we had a long talk about a very personal matter that affects me and could have a direct impact on hundreds of CLL patients. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">Dr. Byrd recently accepted the position of Chairman of the Department of Internal Medicine at the University of Cincinnati and will be starting there on July 1, 2021. The University of Cincinnati press release can be found </span><a href="https://www.uc.edu/news/articles/2021/03/dr-john-byrd-named-chair-of-uc-department-of-internal-medicine.html" style="color: #954f72;"><span style="font-family: Arial, sans-serif;">here</span></a><span style="font-family: Arial, sans-serif;">. Dr. Byrd has been at Ohio State University (OSU) for the past 20 years building a strong team focused on research, clinical trials, and care of patients with CLL and other blood cancers.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">The OSU CLL team has contributed to improving outcomes for all of us in moving forward with therapies such as ibrutinib, acalabrutinib, and novel drug combinations. Dr. Byrd also has been a mentor to many CLL physicians, best exemplified by the excellent research and clinical care being led by his younger colleagues who will continue carrying out the great work at OSU.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">In discussing the reason for the change with Dr. Byrd, it became clear that he is going to the University of Cincinnati with a renewed sense of personal excitement to grow personally as a leader and build an impactful program there that will benefit the lives of many dealing with cancer. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">Dr. Byrd told me how appreciative he was of the years spent at OSU and all the support he received. At the same time, he shared that he realized his personal need for reinvigoration and to make an even bigger impact in the cancer community that he is hoping the University of Cincinnati will provide. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">The University of Cincinnati is next door to the Cincinnati Children’s Hospital and Research Institute, which has the nation’s top pediatric cancer program. The close proximity and relationship will create the perfect opportunity to build bridge programs in multiple areas. This will impact the ability to accelerate new discoveries that will translate to adult cancer patients, which can then be redirected seamlessly back to children’s cancer. The Cincinnati area is the largest US city that does not have a cancer center that has been designated by the</span> <span style="font-family: Arial, sans-serif;">National Cancer Institute (NCI). <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">Working with the team at the Barrett Cancer Center in Cincinnati, Dr. Byrd will continue his work in early drug development and translational laboratory research for CLL and other types of cancer. He will also continue expanding precision medicine in blood cancer and be continually reinforcing the charge for empathetic patient-focused care.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">Dr. Byrd will continue seeing patients with CLL and other blood cancers as a consultant to other physicians, as a CLL and blood cancer expert collaborating with local doctors on yearly visits (as he has done with many patients over the years), and by providing direct care to CLL patients in Cincinnati. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">While there have been rumors that Dr. Byrd will stop seeing patients, in my discussion with him he assured me that this remains the most exciting and favorite part of his job. He is already working on the paperwork for clinical privileges there and hopes to be active in the clinic by August of this year. He is also excited to have some ability to see Veterans Administration patients since the University of Cincinnati has an associated VA Hospital, unlike OSU. From the time of his military service, Dr. Byrd has had a strong commitment to supporting soldiers and veterans alike. He will continue working with new clinical trials that will be available for his patients to match the expectations he established at OSU. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">He told me that his greatest regret of transitioning to the University of Cincinnati is leaving many patients in Columbus with whom he has established long-term patient relationships. While Dr. Byrd is very comfortable with the abilities of the CLL team at OSU following up on his active patient panel (Drs. </span><a href="https://cancer.osu.edu/find-a-doctor/search-physician-directory/jennifer-a-woyach" style="color: #954f72;"><span style="font-family: Arial, sans-serif;">Jennifer Woyack</span></a><span style="font-family: Arial, sans-serif;">, </span><a href="https://cancer.osu.edu/find-a-doctor/search-physician-directory/kerry-rogers" style="color: #954f72;"><span style="font-family: Arial, sans-serif;">Kerry Rogers</span></a><span style="font-family: Arial, sans-serif;">, </span><a href="https://cancer.osu.edu/find-a-doctor/search-physician-directory/adam-s-kittai" style="color: #954f72;"><span style="font-family: Arial, sans-serif;">Adam Kittai</span></a><span class="MsoHyperlink" style="color: #0563c1; text-decoration: underline;"><span style="font-family: Arial, sans-serif;">,</span></span><span style="font-family: Arial, sans-serif;"> and </span><a href="https://cancer.osu.edu/find-a-doctor/search-physician-directory/seema-a-bhat" style="color: #954f72;"><span style="font-family: Arial, sans-serif;">Seema Bhat</span></a><span style="font-family: Arial, sans-serif;">), he is openly welcoming those who decide to follow him to Cincinnati. Dr. Byrd intends to continue collaborating with the CLL team at OSU as well as other individuals (Drs. Jennifer Brown, Deepa Samath, Farrukh Awan, and Deborah Stephens) with whom he has worked over the past two decades on different projects. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">During my discussion with Dr. Byrd, I sensed his excitement about this upcoming transition, the chance to build a new cancer center and to do something special that has the potential to be even more impactful for cancer patients in general, and particularly CLL patients in the future. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 15.693333625793457px; margin: 0in 0in 8pt;"><span style="font-family: Arial, sans-serif;">On a personal note, while Dr. Byrd may be taking on new responsibilities across all internal medicine, after our conversation I felt reassured that he will still be directly caring for and researching the best cutting-edge therapies in CLL for myself and all of us for many years to come.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: normal; margin: 0in;"><span style="font-family: Arial, sans-serif;">Stay strong. We are all in this together.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: normal; margin: 0in;"><span style="font-family: Arial, sans-serif;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: normal; margin: 0in;"><span style="font-family: Arial, sans-serif;">Brian Koffman MDCM (retired) MS Ed<o:p></o:p></span></p><span style="font-family: Arial, sans-serif; font-size: 11pt; line-height: 15.693333625793457px;">Co-Founder, Executive VP and Chief Medical Officer<br />CLL Society</span><span style="font-family: Arial, sans-serif; font-size: 12pt; line-height: 17.1200008392334px;"> <br /><br /></span><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-7238315607560212342021-01-25T14:32:00.006-08:002021-01-25T14:39:41.419-08:00The passing of a CLL pioneer and hero: Joe Greenblatt<p style="text-align: center;"><br /></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhIR1QHkCFdT_v_4EoB5b1LNIvwh0_GmWMVZPRjyRmnx2x5WTgjyonX5Nx4VaIVxgING8PWrLDkeldaYHovFtWYL23_mrLNZto8S8htVh13BeJJ9HetvMqCiScAGsGgAjsG1BCDI_lf3zc/s264/Screen+Shot+2021-01-25+at+11.57.57+AM.png" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="256" data-original-width="264" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhIR1QHkCFdT_v_4EoB5b1LNIvwh0_GmWMVZPRjyRmnx2x5WTgjyonX5Nx4VaIVxgING8PWrLDkeldaYHovFtWYL23_mrLNZto8S8htVh13BeJJ9HetvMqCiScAGsGgAjsG1BCDI_lf3zc/s0/Screen+Shot+2021-01-25+at+11.57.57+AM.png" /></a></div><br /><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">Sad news.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">My long time CLL buddy and a founding member of the </span><a href="https://cllsociety.org/about-us/patient-advisory-board/" style="color: #954f72;"><span style="font-family: inherit, serif; font-size: 11.5pt;">CLL Society Patient Advisory Board</span></a><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">, Joe </span><span style="color: #050505; font-family: inherit, serif;">Greenblatt</span><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> sailed away on January 23, 2021 after a long struggle with COVID-19. Joe had beaten a coma-inducing West Nile Virus encephalitis years ago, learnt to walk again, but his 3rd time on a ventilator proved too much when his lungs and kidneys ultimately failed him.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">I met Joe more than a dozen years ago when he had the great notion to meet up with fellow CLLers at our homes and share our war stories and insider tips. He realized the uniqueness of CLL and felt that we needed our own support and education group with others who lived with our unique blood cancer. It would be different than other cancer groups. It was to be patient led (no nurses, no social workers) and it would be exclusively for CLL families. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">Three of us first met in his living room. And as the say, the rest is history, with CLL Society’s 38 CLL specific support and education groups engaging nearly 2,000 members across the continent today. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">In recent years, Joe had drifted away from CLL Society though he continued to serve on the </span><a href="https://cllsociety.org/about-us/patient-advisory-board/" style="color: #954f72;"><span style="font-family: inherit, serif; font-size: 11.5pt;">patient advisory board</span></a><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">. His CLL was quiescent and he wanted to spend time with his family and his boat. He was a busy guy. But he was proud of his legacy.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">I will be forever in his debt. And if you enjoy the benefits of one of the CLL Society support groups, you might be too.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">His passing is also a cautionary note in these dangerous times. I beg readers to not let down their guard. There is an unpredictable killer in our midst hunting for its next victims. Foil it with a mask and soap and social distancing. Get vaccinated. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">I mourn his loss. He was a trusted friend who told it like it was, a skilled and competitive sailor, and a pragmatic visionary. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">I hope the winds are filling his sails wherever he is now.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="font-family: inherit, serif; font-size: 11.5pt;">Over the years,</span><span style="color: #954f72; font-family: inherit, serif; font-size: 11.5pt;"> <a href="https://cllsociety.org/" style="color: #954f72;">CLL Society</a></span><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> has grown beyond support groups with live online education, support, research and advocacy services to serve the many unmet needs of the CLL community. But the recognition of those unmet needs all began with a handful of us meeting in each other's living rooms. I am still reminded of it every time I see the faces and hear the questions and concerns of my fellow patients and caregivers whom I am now meeting monthly thorough the magic of ZOOM.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">If you haven’t already joined one of our now virtual monthly support and education groups, find out what you have been missing. Simply click on </span><a href="https://cllsociety.org/cll-specific-patient-support-groups/" style="color: #954f72;"><span style="font-family: inherit, serif; font-size: 11.5pt;">CLL-Specific Patient Support Groups</span></a><span style="font-family: inherit, serif; font-size: 11.5pt;"> to learn more. Do it for Joe and for yourself.<span style="color: #050505;"><o:p></o:p></span></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">Stay strong, stay safe, we are all in this together.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;"> </span></p><p class="MsoNormal" style="font-family: Calibri, sans-serif; font-size: 11pt; margin: 0in 0in 0in 0.5in;"><span style="color: #050505; font-family: inherit, serif; font-size: 11.5pt;">Brian<o:p></o:p></span></p><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com1tag:blogger.com,1999:blog-2741672436160438708.post-38356576791641214402020-08-07T14:08:00.011-07:002020-08-07T14:53:36.363-07:00ASH 2019: Dr. Jennifer Brown on Using Ibrutinib after progressing on Venetoclax for Ibrutinib-Naïve Patients with Chronic Lymphocytic Leukemia (CLL)<p class="MsoNormal" style="font-family: Calibri, sans-serif; margin: 0in;">There has been much discussion, but little data on what is the best order of medications to treat CLL and whether combining drugs is better than sequencing them in the long run. In other words, what is the best way to use all this great drugs to keep us alive the longest.</p><p class="MsoNormal" style="font-family: Calibri, sans-serif; margin: 0in;"><br /></p><p class="MsoNormal"><span style="font-family: helvetica;">At ASH 2019, in Orlando, FL, I interviewed <a href="https://www.dfhcc.harvard.edu/insider/member-detail/member/jennifer-r-brown-md-phd/">Dr. Jennifer Brown</a>, Director of CLL Research at Dana Farber Cancer Institute in Boston and a Professor at Harvard Medical School about her real-world research to gather some data to inform these discussions.</span></p><p class="MsoNormal"><span style="font-family: helvetica;"><br /></span></p><p class="MsoNormal"><span style="font-family: helvetica;">Specifically, Dr. Brown looked at the data for those patients who had taken venetoclax, but not ibrutinib, and then relapsed. The basic question she was asking was how well they did.</span></p><p class="MsoNormal"><span style="font-family: helvetica;"><br /></span></p><p class="MsoNormal"><span style="font-family: helvetica;">Take Aways:<o:p></o:p></span></p><p class="MsoListParagraphCxSpFirst" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span face="" style="font-stretch: normal; line-height: normal;"> </span></span>We have known for some time that venetoclax is a successful salvage therapy for those who fail a BTK inhibitor such as ibrutinib or acalabrutinib. Dr. Wierda was <a href="https://cllsociety.org/2018/08/nccn-hematology-congress-2017-dr-wierda-on-cll-patients-that-progress-on-ibrutinib/">talking about this back in 2017</a>.<o:p></o:p></span></p><p class="MsoListParagraphCxSpFirst" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><br /></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span face="" style="font-stretch: normal; line-height: normal;"> </span></span>We have much less data on the other way around. Now that venetoclax is approved frontline and will likely be increasingly used frontline or in later lines of therapy ahead of a BTK inhibitor, we really do need to know.<o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><br /></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span face="" style="font-stretch: normal; line-height: normal;"> </span></span>Dr. Brown led a group of researchers that retrospectively looked at 27 patients had never been on ibrutinib but who had received venetoclax, but then relapsed or stopped.<o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><br /></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span face="" style="font-stretch: normal; line-height: normal;"> </span></span>On average, venetoclax was the 3<sup>rd</sup> line of treatment for these patients, so ibrutinib would be the 4<sup>th</sup>, a tough group to treat.<o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><br /></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span face="" style="font-stretch: normal; line-height: normal;"> </span></span>Risk factors for progression on venetoclax were as expected: del 17p (4/10; 40.0%), del 11q (4/9; 44.4%), complex karyotype (8/17; 47.1%) and unmutated IGHV (11/14; 78.6%). For more on these tests, see our Test Before Treat Section.<o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><br /></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span face="" style="font-stretch: normal; line-height: normal;"> </span></span>56% or 14 of the 27 patients responded to ibrutinib with one achieving a complete remission.<o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><br /></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span face="" style="font-stretch: normal; line-height: normal;"> </span></span><span style="background-color: white; background-position: initial initial; background-repeat: initial initial; color: #1a1a1a;">The time to progression on ibrutinib post-venetoclax varied from 3.0 to 53.0 months.</span><span face=""><o:p></o:p></span></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><span style="background-color: white; background-position: initial initial; background-repeat: initial initial; color: #1a1a1a;"><br /></span></span></p><p class="MsoListParagraphCxSpLast" style="mso-list: l0 level1 lfo1; text-indent: -0.25in;"><span style="font-family: helvetica;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;">·<span face="" style="font-stretch: normal; line-height: normal;"> </span></span>Slightly less than half of the ibrutinib patients who stopped did so because of progressive disease (PD). </span></p><p class="MsoNormal"><span style="font-family: helvetica;"><br /></span></p><p class="MsoNormal"><span style="font-family: helvetica;">Conclusion:</span></p><p class="MsoNormal"><span style="font-family: helvetica;"><br /></span></p><p class="MsoNormal"><span style="font-family: helvetica;">We know there is life after ibrutinib. Now we know that there is at least one good option after ibrutinib, at least for those who have never been on it before.</span></p><p class="MsoNormal"><span style="font-family: helvetica;"><br /></span></p><p class="MsoNormal"><span style="font-family: helvetica;">What we don’t know is what is the best sequencing of the good drugs that we have. All drugs work best when used as the first therapy, but which order is the best. </span></p><p class="MsoNormal"><span style="font-family: helvetica;"><br />For more, please enjoy my interview from ASH 2019 with Dr. Brown <a href="https://youtu.be/UcVbcAX4UbI">here</a>.</span></p><p class="MsoNormal"><span style="font-family: helvetica;"><br /></span></p><p class="MsoNormal"><span style="font-family: helvetica;">For more of the details, please take a look at the abstract itself: <a href="https://ashpublications.org/blood/article/134/Supplement_1/4320/424630/Outcomes-of-Ibrutinib-Ibr-Therapy-in-Ibr-Naive">Outcomes of Ibrutinib Therapy in Ibrutinib-Naïve Patients with Chronic Lymphocytic Leukemia (CLL) Progressing after Venetoclax</a>.</span></p><p class="MsoNormal"><span style="font-family: helvetica;"><br /></span></p><p class="MsoNormal"><span style="font-family: helvetica;">For a different perspective on this same sequencing issue, see my interview with Dr. Mato from the same ASH 2019<a href="https://cllsociety.org/2020/02/ash-2019-dr-mato-on-sequencing-of-chronic-lymphocytic-leukemia-cll-therapies-after-venetoclax/">: </a><a href="https://cllsociety.org/2020/02/ash-2019-dr-mato-on-sequencing-of-chronic-lymphocytic-leukemia-cll-therapies-after-venetoclax/">Dr. Mato on Sequencing of Chronic Lymphocytic Leukemia (CLL) therapies after Venetoclax.</a></span></p><p class="MsoNormal"><br /></p><p class="MsoNormal"><span style="font-family: helvetica;">Stay strong, </span></p><p class="MsoNormal"><span style="font-family: helvetica;">We are all in this together<o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: helvetica;">Brian</span></p><style class="WebKit-mso-list-quirks-style">
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</style><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com3tag:blogger.com,1999:blog-2741672436160438708.post-82785924530432284052019-08-04T13:09:00.001-07:002019-08-04T13:16:08.919-07:00ASH 2018: Dr. Neil Kay on how Stromal Cells Keep CLL (chronic lymphocytic leukemia) Cells Alive in the Bone Marrow and How we Can Intervene<div class="MsoNormal" style="color: black; font-style: normal; font-weight: normal; letter-spacing: normal; margin: 0in 0in 0.0001pt; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; word-spacing: 0px;">
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<span style="font-family: Arial, Helvetica, sans-serif;"><span style="font-family: "calibri" , sans-serif; font-size: 11pt;">At ASH 2018 in San Diego, CA, I interviewed</span><span style="font-family: "calibri" , sans-serif; font-size: 11pt;"> </span><a href="https://www.mayo.edu/research/faculty/kay-neil-e-m-d/bio-00027763" style="font-family: Calibri, sans-serif; font-size: 11pt;">Dr. Neil Kay</a><span style="font-family: "calibri" , sans-serif; font-size: 11pt;"> </span><span style="font-family: "calibri" , sans-serif; font-size: 11pt;">out of Mayo Clinic, Rochester, MN, an innovative chronic lymphocytic leukemia researcher who besides caring for CLL patients and doing clinical trials, is doing important “bench” science where when we are fortunate we can find insights that can transform how we can best knock out the CLL cells.</span></span></div>
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<span style="font-family: Arial, Helvetica, sans-serif; font-size: 11pt;">Dr. Kay’s research presented at ASH 2018 was on the supportive stromal cells in the bone marrow, formally known as mesenchymal stromal cells (MSCs).<o:p></o:p></span></div>
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<span style="font-family: Arial, Helvetica, sans-serif; font-size: 11pt;">Takeaways:<o:p></o:p></span></div>
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<!--[if !supportLists]--><span style="font-family: Arial, Helvetica, sans-serif;"><span style="font-family: "symbol"; font-size: 11.0pt;"><span style="mso-list: Ignore;">·<span style="font-stretch: normal; font-style: normal; font-variant-caps: normal; font-weight: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-size: 11pt;">Stromal cells are part of a network of cells in the bone marrow that help keep CLL cells from dying.<o:p></o:p></span></span></div>
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<!--[if !supportLists]--><span style="font-family: Arial, Helvetica, sans-serif;"><span style="font-family: "symbol"; font-size: 11.0pt;"><span style="mso-list: Ignore;">·<span style="font-stretch: normal; font-style: normal; font-variant-caps: normal; font-weight: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-size: 11pt;">Dr. Kay’s lab has built a model of MSCs supporting CLL cells for experimentation. <o:p></o:p></span></span></div>
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<!--[if !supportLists]--><span style="font-family: Arial, Helvetica, sans-serif;"><span style="color: black; font-family: "symbol"; font-size: 11.0pt;"><span style="mso-list: Ignore;">·<span style="font-stretch: normal; font-style: normal; font-variant-caps: normal; font-weight: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="color: black; font-size: 11pt;">They discovered that the </span><span style="background-color: white; color: black;">marrow stromal cell mediated i</span><span style="-webkit-text-stroke-width: 0px; caret-color: rgb(79, 79, 79); float: none; font-variant-caps: normal; text-align: start; word-spacing: 0px;">ncreased expression in two enzymes, β-catenin and Axl in CLL B-cells is associated with leukemic cell survival and drug resistance.</span><span class="apple-converted-space"><span style="-webkit-text-stroke-width: 0px; caret-color: rgb(79, 79, 79); float: none; font-variant-caps: normal; text-align: start; word-spacing: 0px;"> </span></span><span style="color: black; font-size: 11pt;"><o:p></o:p></span></span></div>
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<!--[if !supportLists]--><span style="font-family: Arial, Helvetica, sans-serif;"><span style="font-family: "symbol"; font-size: 11.0pt;"><span style="mso-list: Ignore;">·<span style="font-stretch: normal; font-style: normal; font-variant-caps: normal; font-weight: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="background-color: white; color: black;">The experimental drug, TP-0903 blocks Axl and reduces CLL cells’ survival and their ability to resist chemotherapy.</span><span style="font-size: 11pt;"><o:p></o:p></span></span></div>
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<span style="color: #111111; font-family: Arial, Helvetica, sans-serif; font-size: 11pt;">Conclusions:<o:p></o:p></span></div>
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<span style="color: #111111; font-family: Arial, Helvetica, sans-serif; font-size: 11pt;">It is easy to forget that ibrutinib was only developed as the amazing breakthrough for chronic lymphocytic leukemia it is when the importance of the B-cell receptor (BCR) to CLL cells survival was recognized, in other words when that biology was cracked.<o:p></o:p></span></div>
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<span style="color: #111111; font-family: Arial, Helvetica, sans-serif; font-size: 11pt;">Dr. Kay and his team is trying to do the same kind of thing with this research and it has quickly gone from bench to bedside in a clinical trial using TP-0903 alone or in combination with ibrutinib: <b><a href="https://clinicaltrials.gov/ct2/show/NCT03572634" style="color: #954f72; text-decoration: underline;">Phase 1/2 Study of TP-0903 (an Inhibitor of AXL Kinase) in Patients With Previously Treated CLL</a>.<o:p></o:p></b></span></div>
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<span style="color: #111111; font-family: Arial, Helvetica, sans-serif; font-size: 11pt;">It is an intriguing direction, attacking the soil, not just the seed of cancer. For more of the importance of cancer micro-environment, see my <a href="https://cllsociety.org/2019/07/ash-2018-dr-yucai-wang-on-the-micro-environment-in-cll-chronic-lymphocytic-leukemia/" style="color: #954f72; text-decoration: underline;">interview with Dr. Wang</a>, also from Mayo.<o:p></o:p></span></div>
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<span style="color: #111111; font-family: Arial, Helvetica, sans-serif; font-size: 11pt;">While the science may be less accessible than we talk about clinical trial results, there would be no new drugs for clinical trials without this basic laboratory research.<o:p></o:p></span></div>
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<span style="color: #111111; font-family: Arial, Helvetica, sans-serif; font-size: 11pt;">Here is my ASH 2018 interview with Dr. Kay.<o:p></o:p></span></div>
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<span style="font-family: Arial, Helvetica, sans-serif; font-size: 11pt;">Here is the actual <a href="http://www.bloodjournal.org/content/132/Suppl_1/3125" style="color: #954f72; text-decoration: underline;">abstract</a>.<o:p></o:p></span><br />
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<span style="font-family: "calibri" , sans-serif; font-size: 11pt;">Thanks for reading</span></span><br />
<span style="font-family: Arial, Helvetica, sans-serif;"><span style="font-family: "calibri" , sans-serif; font-size: 11pt;"><br /></span>
<span style="font-family: "calibri" , sans-serif; font-size: 11pt;">Brian Koffman</span></span></div>
<div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-9893225719056859282019-07-13T21:06:00.001-07:002019-07-13T21:06:27.349-07:00So tired<div class="MsoNormal" style="font-family: Calibri, sans-serif; margin: 0in 0in 0.0001pt;">
So tired.<o:p></o:p></div>
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I have been tired and sleepy for weeks now. Which is weird as my CLL is in a deep deep deep remission.<o:p></o:p></div>
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I first blamed it on stress- have a googol of problems weighing on me, but I usually cope well with pressure. <o:p></o:p></div>
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Been traveling >100,000 miles in the last 6 months including 2 hectic sleep robbing trips to Europe to lecture on chronic lymphocytic leukemia or CLL in June so I thought maybe jet lag. But I’ve been home for 10 days now, so that should have resolved by now.<o:p></o:p></div>
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Have an 18-wheeler full of to -dos ahead of me, but that isn’t all that unusual. One at a time is my mantra.<o:p></o:p></div>
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Been in increased pain due to my bone on bone osteoarthritic knees. I had a scare yesterday when I developed increased right calf pain and swelling in my foot. A quick Doppler showed no blood clot, but I do have significant excess fluids in my calf likely due to my arthritis and swelling around the knee. Pain can wear anyone down, but I am used to low grade pain.<o:p></o:p></div>
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Blood pressure and pulse are low normal and I don’t feel sick.<o:p></o:p></div>
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My labs are all great, not anemic, CLL is no where to be seen in the blood and no enlarged nodes. Blood chemistries are fine except for low protein. I do have some elevated inflammatory markers that don’t help my energy.<o:p></o:p></div>
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Checked my thyroid and it’s normal too. I don’t snore, so I doubt I have sleep apnea.<o:p></o:p></div>
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Tried my usual remedies- sleeping in, naps, dark chocolate, more exercise, less food, change of scenery. No help. Some ice coffee helps for a few hours.<o:p></o:p></div>
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Now I switching to less swimming and more weight training, no naps and going to bed early.<o:p></o:p></div>
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And working anyway. <o:p></o:p></div>
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This too will pass.<o:p></o:p></div>
<div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-60196992260241800512019-05-22T19:21:00.001-07:002019-05-22T19:21:01.995-07:00 May 15, 2019: FDA approved venetoclax in combination with obinutuzumab for the treatment of people with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
This is very big news.</div>
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This is the first non-chemotherapy based fixed duration treatment for CLL in treatment naïve patients.</div>
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Until this approval, the only viable approved treatments were fixed duration chemotherapy or taking ibrutinib until progression or side effects force you off.</div>
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Of course, venetoclax and obinutzumab could have been and have been used together “off label” as they are both already approved medications, but now insurance will have no excuse not to pay for it. And doctors less familiar with treating CLL should feel comfortable with an another strong option for a first therapy.</div>
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The <a href="https://cllsociety.org/2016/03/trial-phases/" style="color: #52adad; margin: 0px; padding: 0px;">Phase III study</a> was done by the well-respected German CLL study group lead by Prof. Hallek out of Cologne.</div>
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Here is a link to the <a href="https://news.abbvie.com/news/press-releases/abbvie-announces-us-fda-approval-venclexta-venetoclax-as-chemotherapy-free-combination-regimen-for-previously-untreated-chronic-lymphocytic-leukemia-patients.htm" rel="noopener noreferrer" style="color: #52adad; margin: 0px; padding: 0px;" target="_blank">Abbvie press release</a>.</div>
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Below is part of the press release from Genentech who is co-developing venetoclax with Abbvie</div>
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<span style="font-weight: 700; margin: 0px; padding: 0px;">About the CLL14 Study</span></div>
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CLL14 (NCT02242942) is a randomized Phase III study evaluating the combination of fixed-duration venetoclax plus obinutuzumab compared to obinutuzumab plus chlorambucil in patients with previously untreated chronic lymphocytic leukemia (CLL) and co-existing medical conditions. 432 patients with previously untreated CLL were randomly assigned to receive either a 12-month duration of Venetoclax alongside six-month duration of Obinutuzumab (Arm A) or six-month duration of obinutuzumab plus chlorambucil followed by an additional six-month duration of chlorambucil (Arm B). Arm A started with an initial cycle of obinutuzumab followed by a five-week venetoclax dose ramp-up to help reduce tumor burden. The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints include PFS assessed by Independent Review Committee (IRC), minimal residual disease (MRD) status, overall response (OR), complete response (with or without complete blood count recovery, CR/CRi), overall survival (OS), duration of response (DOR), event-free survival (EFS), time to next CLL treatment (TTNT), and safety. The CLL14 study is being conducted in cooperation with the German CLL Study Group (GCLLSG), headed by Michael Hallek, M.D., University of Cologne.</div>
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<a class="dt-single-image mfp-ready" data-dt-img-description="" href="https://cllsociety.org/wp-content/uploads/2019/05/CLL14_Study_Results_.png" style="color: #52adad; margin: 0px; padding: 0px;"><img alt="" class="aligncenter wp-image-11053 retinized" height="571" sizes="(max-width: 738px) 100vw, 738px" src="https://cllsociety.org/wp-content/uploads/2019/05/CLL14_Study_Results_-1024x793.png" srcset="https://cllsociety.org/wp-content/uploads/2019/05/CLL14_Study_Results_-1024x793.png 1024w, https://cllsociety.org/wp-content/uploads/2019/05/CLL14_Study_Results_-300x232.png 300w, https://cllsociety.org/wp-content/uploads/2019/05/CLL14_Study_Results_-768x595.png 768w, https://cllsociety.org/wp-content/uploads/2019/05/CLL14_Study_Results_.png 1542w" style="border: 0px; display: block; height: auto; margin: 0px auto 10px; max-width: 100%; padding: 0px; transition: opacity 1000ms ease;" width="738" /></a></div>
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The most common adverse reactions with Venetoclax plus Obinutuzumab were low white blood cell count (neutropenia), diarrhea, fatigue, nausea, low red blood cell count (anemia), and upper respiratory tract infection.</div>
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Comments:</div>
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This is a powerful new option for patients to consider. Just how durable these responses will be remains to be determined, but the depth of the remissions with ¾ of patients reaching U-MRD (undetectable minimal disease or less than one CLL cell per 10,000 white blood cells) in the peripheral blood and 56% in the bone marrow bodes well for lengthy responses. For more on MRD from Prof. Hallek , see this <a href="https://cllsociety.org/2018/09/ash-2017-atlanta-professor-michael-hallek-on-mrd-negativity-in-cll/" style="color: #52adad; margin: 0px; padding: 0px;">interview from ASH 2017</a>. What we patients want to see if very durable PFS (progression fee survival) and OS (overall survival), and the early results are promising.</div>
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Moreover, hopefully this is the first of many such approvals of fixed duration combinations that will be coming over the next few years that could revolutionize how CLL is treated. And of course, the approval raises the question as to which combos and sequences are best.</div>
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Exciting times for us patients.</div>
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Brian Koffman, Chief Medical Officer, CLL Society</div>
<br class="Apple-interchange-newline" /><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-50190084623143427052019-05-12T14:40:00.001-07:002019-05-12T14:40:22.800-07:00Acalabrutinib Phase III ASCEND trial met primary endpoint at interim analysis in relapsed or refractory chronic lymphocytic leukemia and will stop early<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
This trial in previously treated CLL patients showed a clinically significant progression free survival when compared to a combination regimen of rituximab plus physician’s choice of idelalisib or bendamustine. No new side effects or problems were noted.</div>
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While not unexpected, it is important to have this trial confirmation that another BTK inhibitor, like ibrutinib has proven to save lives.</div>
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This is more good news for CLL patients. Acalabrutinib is already approved for mantle cell lymphoma (MCL) and hopefully will be soon approved for us CLL patients based on this and Phase 3 trials that should have positive results soon.</div>
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While not approved for CLL, because it is approved for MCL and is part of the NCCN guidelines for CLL, it is already an option today for appropriate CLL patients if your doctor pushes for it.</div>
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Here is a <a href="https://www.onclive.com/web-exclusives/acalabrutinib-improves-pfs-in-relapsed-refractory-cll" rel="noopener noreferrer" style="color: #52adad; margin: 0px; padding: 0px;" target="_blank">link</a> to a nice review of the data we have so far and more trial news.</div>
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Here is the official <a href="https://www.astrazeneca.com/media-centre/press-releases/2019/calquence-phase-iii-ascend-trial-met-primary-endpoint-at-interim-analysis-in-relapsed-or-refractory-chronic-lymphocytic-leukaemia-and-will-stop-early-07052019.html#!" rel="noopener noreferrer" style="color: #52adad; margin: 0px; padding: 0px;" target="_blank">press release</a>.</div>
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It is good to have more choices of all these great drugs. Can’t wait for approval to make it easier to access.</div>
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Stay strong,</div>
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Brian</div>
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Brian Koffman MDCM DCFP, DABFM, MS Ed<br style="margin: 0px; padding: 0px;" />Co-Founder, Executive VP and Chief Medical Officer<br style="margin: 0px; padding: 0px;" />CLL Society, Inc.</div>
<br class="Apple-interchange-newline" /><div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com1tag:blogger.com,1999:blog-2741672436160438708.post-6809149357519871712019-03-26T23:19:00.001-07:002019-03-26T23:19:22.144-07:00One Year CAR-T Anniversary to Treat my CLL and an Interview with Dr. Siddiqi about how chronic lymphocytic leukemia treatment has change since ASH 2018<div style="box-sizing: border-box; caret-color: rgb(42, 42, 42); color: #2a2a2a; font-family: FixEmoji, "Open Sans", "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15px; margin-bottom: 10.5px;">
Hi</div>
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March 22, 2019 was my one year anniversary of receiving my experimental CAR-T cells in Seattle.</div>
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About a month earlier, I got the great news that I remain U-MRD4 in the peripheral blood- no CLL to be found. Read more here: <a href="https://cllsociety.org/2019/03/one-year-anniversary/">https://cllsociety.org/2019/03/one-year-anniversary/</a></div>
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Also this week, I posted a brief ASH 2018 interview with Dr. Siddiqi that hits the important practice changing data that emerged from ASH 2018. See: <a href="https://cllsociety.org/2019/03/ash-2018-dr-siddiqi-on-the-practice-changing-lessons-for-treating-cll/">https://cllsociety.org/2019/03/ash-2018-dr-siddiqi-on-the-practice-changing-lessons-for-treating-cll/</a></div>
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Enjoying a total of two weeks at home before I head to Bethesda for our educational forum at the NIH on April 5. Hope to see some of you there.</div>
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Stay strong.</div>
<div style="box-sizing: border-box; caret-color: rgb(42, 42, 42); color: #2a2a2a; font-family: FixEmoji, "Open Sans", "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15px; margin-bottom: 10.5px;">
We are all in this together.</div>
<div style="box-sizing: border-box; caret-color: rgb(42, 42, 42); color: #2a2a2a; font-family: FixEmoji, "Open Sans", "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15px; margin-bottom: 10.5px;">
Brian</div>
<div style="box-sizing: border-box; caret-color: rgb(42, 42, 42); color: #2a2a2a; font-family: FixEmoji, "Open Sans", "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15px; margin-bottom: 10.5px;">
Brian Koffman MDCM DCFP, DABFM, MS Ed</div>
<div style="box-sizing: border-box; caret-color: rgb(42, 42, 42); color: #2a2a2a; font-family: FixEmoji, "Open Sans", "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15px; margin-bottom: 10.5px;">
Co-Founder, Executive VP and Chief Medical Officer</div>
<div style="box-sizing: border-box; caret-color: rgb(42, 42, 42); color: #2a2a2a; font-family: FixEmoji, "Open Sans", "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15px; margin-bottom: 10.5px;">
CLL Society, Inc.</div>
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<a href="http://cllsociety.org/">CLLSociety.org</a></div>
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PO Box 1390</div>
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Claremont, CA 91711</div>
<div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-74213400843257874752019-02-16T22:44:00.003-08:002019-02-16T22:59:31.752-08:00CMS Approval of CAR-T Therapy<div class="" data-block="true" data-editor="fcrda" data-offset-key="c2luj-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
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<span data-offset-key="c2luj-0-0" style="font-family: inherit;">CMS approves CAR-T therapy payment, but with significant strings attached. For more details see: <a href="https://cllsociety.org/2019/02/cms-approves-car-t-therapy-payment/">https://cllsociety.org/2019/02/cms-approves-car-t-therapy-payment/</a></span></div>
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<span data-offset-key="1b44t-0-0" style="font-family: inherit;">This is a positive first step, but only the first step. We will be interviewing experts on funding over the next few weeks.</span></div>
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<span data-offset-key="9cmbd-0-0" style="font-family: inherit;">I am proud of the small role I played in this by going to CMS and lobbying on behalf of future CAR-T patients.</span><br />
<span style="font-family: inherit;">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. </span><br />
<span style="font-family: inherit;">Thanks. Stay strong. After all, we are all in this together. </span><br />
<span style="font-family: inherit;">And please visit our website: http://cllsociety.org for the latest news and information.</span><br />
<span data-offset-key="9cmbd-0-0" style="font-family: inherit;">Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.</span></div>
</div>
<div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com2tag:blogger.com,1999:blog-2741672436160438708.post-2346934573984283452019-01-29T23:59:00.005-08:002019-01-29T23:59:50.584-08:00The evolving role of clinical trials in CLL (chronic lymphocytic leukemia)<div class="MsoNormal" style="font-family: Calibri, sans-serif; margin: 0in 0in 0.0001pt;">
<span style="font-size: 11pt;">Hi,<o:p></o:p></span></div>
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<span style="font-size: 11pt;">As many of you know, I am alive today because of my entering two phase I clinical trials, one for PCI-32765 that later became known as ibrutinib and another for a CAR-T drug.<o:p></o:p></span></div>
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<span style="font-size: 11pt;">Clinical trials are always great, right?<br /><br />Well Dr. Furman has a more nuanced answer to that from our interview at ASH 2018. And he is clearly putting the patient first.<o:p></o:p></span></div>
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<span style="font-size: 11pt;">No-one is saying that clinical trials are not the best source of evidence, but what questions are being answered and at what cost to patients need to be carefully considered.<o:p></o:p></span></div>
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<span style="font-size: 11pt;">See: <a href="https://cllsociety.org/2019/01/ash-2018-dr-furman-on-the-evolving-role-of-clinical-trials-in-cll/"><span style="color: #954f72;">https://cllsociety.org/2019/01/ash-2018-dr-furman-on-the-evolving-role-of-clinical-trials-in-cll/</span> </a>for the interview.<o:p></o:p></span></div>
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<span style="font-size: 11pt;">Lots more news on the website. Hard to keep up<o:p></o:p></span></div>
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<span style="font-size: 11pt;">And please don’t forget to register our upcoming educational forums in Duarte, Charlotte, Seattle, Portland and Houston in the next 60 days.<o:p></o:p></span></div>
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<a href="https://www.blogger.com/null" name="_MailAutoSig"><span style="font-size: 11pt;">Stay strong.<o:p></o:p></span></a></div>
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<span style="font-size: 11pt;">We are all in this together.<o:p></o:p></span></div>
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<span style="font-size: 11pt;">Brian </span><span style="font-size: 11pt;"><o:p></o:p></span></div>
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<span style="font-size: 11pt;">Cllsociety.org</span></div>
<div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-8228493254241109612019-01-22T23:14:00.003-08:002019-01-22T23:14:43.596-08:00Upcoming free CLL Specific Educational Forums for Patients and Caregivers Across the USA<div style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; margin-bottom: 6px;">
We will be holding a total of a dozen free CLL specific ½ day Educational Forums for patients and caregivers across the country over the next few months. These will cover everything from the basics to the latest research from ASH presented by the local faculty with sessions by patients too. Each one is a little different, as we rely on the local experts to talk about their CLL strengths and research.</div>
<div style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; margin-bottom: 6px; margin-top: 6px;">
The next one is in Duarte, CA with faculty from City of Hope on Feb. 9, then<span class="text_exposed_show" style="display: inline; font-family: inherit;"> Feb 23 in Charlotte, NC, then Seattle, March 2 and Portland, March 9. I will be at all of these, speaking on being our own advocates and would love it you could attend and say hello. For more info and to register, please go to: <a data-ft="{"tn":"-U"}" data-lynx-mode="origin" href="https://l.facebook.com/l.php?u=https%3A%2F%2Fcllsociety.org%2Fpatient-education-forums-coming-soon%2F%3Ffbclid%3DIwAR1-cEwTbP6Cbv4eQTROjrWyetdxazKj4FH8DgyQByrkU12IJ7AGA8bSkWg&h=AT0VE9D-2iau4sxhQcUu4A4e6uH7G6p2ZupH5qQvRD8rFxW-ipC6oi8Vccy5lLx6S1g2HBROryNQpeNFj_Tb8wEhBjmfUxNwlwHk2QbPy0yxugBfFUaYa9BLjzCtp7gHT7lA-XMgUXrL-q4F01urixAOX74" rel="noopener nofollow" style="color: #365899; cursor: pointer; font-family: inherit; text-decoration: none;" target="_blank">https://cllsociety.org/patient-education-forums-coming-soon/</a></span></div>
<div class="text_exposed_show" style="caret-color: rgb(29, 33, 41); color: #1d2129; display: inline; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px;">
<div style="font-family: inherit; margin-bottom: 6px;">
Later we will be at MDACC in Houston, the NIH in Bethesda, Mayo in Minneapolis and more. </div>
<div style="font-family: inherit; margin-bottom: 6px; margin-top: 6px;">
Stay strong.</div>
<div style="font-family: inherit; margin-bottom: 6px; margin-top: 6px;">
We are all in this together.</div>
<div style="font-family: inherit; margin-bottom: 6px; margin-top: 6px;">
Brian Koffman</div>
</div>
<div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-30845773326687260512018-12-29T13:05:00.006-08:002018-12-29T13:10:44.333-08:00Reflections on year of both great progress and great sadness in the CLL world<div class="" data-block="true" data-editor="fhc0f" data-offset-key="b5e9i-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
</div>
<div class="" data-block="true" data-editor="fhc0f" data-offset-key="f9355-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
<div class="_1mf _1mj" data-offset-key="f9355-0-0" style="direction: ltr; font-family: inherit; position: relative;">
<span data-offset-key="f9355-0-0" style="font-family: inherit;">Happy New Year.</span></div>
</div>
<div class="" data-block="true" data-editor="fhc0f" data-offset-key="qvl1-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
<div class="_1mf _1mj" data-offset-key="qvl1-0-0" style="direction: ltr; font-family: inherit; position: relative;">
<span data-offset-key="qvl1-0-0" style="font-family: inherit;">This year we lost 3 members of our local Orange County CLL Society support group, and I lost other 3 other dear CLL and CAR-T friends that I met on my personal journey.</span></div>
</div>
<div class="" data-block="true" data-editor="fhc0f" data-offset-key="a98ol-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
<div class="_1mf _1mj" data-offset-key="a98ol-0-0" style="direction: ltr; font-family: inherit; position: relative;">
<span data-offset-key="a98ol-0-0" style="font-family: inherit;">So sad. My heart still aches. CLL is still a killer. We all know too many tragedies and too many close calls and too many living in fear.</span></div>
</div>
<div class="" data-block="true" data-editor="fhc0f" data-offset-key="5e3lg-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
<div class="_1mf _1mj" data-offset-key="5e3lg-0-0" style="direction: ltr; font-family: inherit; position: relative;">
<span data-offset-key="5e3lg-0-0" style="font-family: inherit;">We at the nonprofit CLL Society have ambitions to change that through targeted research as funding for CLL studies is starting to dry up. It’s largely seen as a solved problem. That is a tragic joke that we will work with LLS, others and our fellow CLL survivor to help correct. Stay tuned. We are working with top researchers to be smart about how to marshal our limited resources</span></div>
</div>
<div class="" data-block="true" data-editor="fhc0f" data-offset-key="a43oo-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
<div class="_1mf _1mj" data-offset-key="a43oo-0-0" style="direction: ltr; font-family: inherit; position: relative;">
<span data-offset-key="a43oo-0-0" style="font-family: inherit;">Today our biggest push remains to ensure that everyone gets their best possible care by getting smart about their CLL. That is what blogs such as this do.</span></div>
</div>
<div class="" data-block="true" data-editor="fhc0f" data-offset-key="7ofre-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
<div class="_1mf _1mj" data-offset-key="7ofre-0-0" style="direction: ltr; font-family: inherit; position: relative;">
<span data-offset-key="7ofre-0-0" style="font-family: inherit;">If you haven’t already, please check out on website. Last week’s newsletter is chock full of helpful info for any CLL patient or caregiver at any point of their journey. </span></div>
</div>
<div class="" data-block="true" data-editor="fhc0f" data-offset-key="dd99v-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
<div class="_1mf _1mj" data-offset-key="dd99v-0-0" style="direction: ltr; font-family: inherit; position: relative;">
<span data-offset-key="dd99v-0-0" style="font-family: inherit;">On Feb. 9 we will hold our first of the year post- ASH educational forum at City of Hope and will live stream it. Registration is now open. 10 more forums will follow across the country.</span></div>
</div>
<div class="" data-block="true" data-editor="fhc0f" data-offset-key="f4g77-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
<div class="_1mf _1mj" data-offset-key="f4g77-0-0" style="direction: ltr; font-family: inherit; position: relative;">
<span data-offset-key="f4g77-0-0" style="font-family: inherit;">The news in 2019 overall has been good with amazing progress, but it is not good enough and not everyone gets the benefits of all the progress.</span></div>
</div>
<div class="" data-block="true" data-editor="fhc0f" data-offset-key="41hk3-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
<div class="_1mf _1mj" data-offset-key="41hk3-0-0" style="direction: ltr; font-family: inherit; position: relative;">
<span data-offset-key="41hk3-0-0" style="font-family: inherit;">Let’s dedicated ourselves to working together. One of our motto for 2019 will be no patient left behind. And of course: Smart patients get smart care.</span></div>
</div>
<div class="" data-block="true" data-editor="fhc0f" data-offset-key="1fvb1-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
<div class="_1mf _1mj" data-offset-key="1fvb1-0-0" style="direction: ltr; font-family: inherit; position: relative;">
<span data-offset-key="1fvb1-0-0" style="font-family: inherit;">Stay strong. We are all in this together.</span></div>
</div>
<div class="" data-block="true" data-editor="fhc0f" data-offset-key="7j6ei-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
<div class="_1mf _1mj" data-offset-key="7j6ei-0-0" style="direction: ltr; font-family: inherit; position: relative;">
<span data-offset-key="7j6ei-0-0" style="font-family: inherit;">Brian </span></div>
</div>
<div class="" data-block="true" data-editor="fhc0f" data-offset-key="26ctf-0-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">
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<span data-offset-key="26ctf-0-0" style="font-family: inherit;">Website: www.cllsociety.org</span></div>
</div>
<div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-84252418753177503812018-12-12T22:47:00.003-08:002018-12-12T22:47:50.968-08:00Closing One Door, Opening Another.<br /><div class="MsoNormal">
December 10, 2018 was a monumental day for me. A huge transition.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
After 38 years of caring for generations of patients as
their family doctor, I retired today from direct patient care. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Bittersweet. Lots of hugs and more than a few tears.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
It’s been a tremendous privilege to care for so many people,
to touch so many lives. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Today, for example, I said goodbye to my 104-year-old patient,
to another long time patient that I had helped decades ago out of downward spiral
to reinvent herself, a married gay man who flew in from Houston to consult me
one last time, a seventy-year-old who reminded me that I caught his cancer
early and likely saved his life over 20 years ago, and a fellow leukemia
patient that I helped with his hospitalization. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Family medicine threw me into the lives of blacks, whites, Latinos,
Asians and others, newborns and the very elderly, nearly every religious group
and agnostics and atheists, too, the fabulously rich and the desperately poor,
the morbidly obese and the anorexic, those with poor health choices and health
fanatics, many omnivores and a few fellow vegans, professional athletes,
weekend warriors and couch potatoes, those with special needs, scientists and poets
and painters, preachers and rabbis, musicians and dancers, lawyers and felons, students
and teachers, fellow doctors, CEOs, factory workers, police and firemen, celebrities,
the homeless and so many more.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
I have dealt with the trivial and the deadly, often on the
same day, often in the same hour.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
I have shared the darkest and happiest moments in some of my
patients’ lives. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
I have shared birth and death, the latter, too often and too
soon for so many.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
I will miss all my patients dearly. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
But I leave that incredible job that has so defined me for
the last 4 decades to care for folks in a different way, to care for a cohort,
to save lives through education, support, advocacy and research that I will be
doing as I move to the CLL Society full time after 4 years of what was
essentially a more than full time unpaid job.<o:p></o:p></div>
<div class="MsoNormal">
I will now work for the CLL Society from 8:00a.m. to
6:00p.m., instead of from 8:00 p.m. to 2:00 a.m., and on the weekends.<span style="mso-spacerun: yes;"> </span>More importantly, in accepting the position
of Chief Medical Officer and Executive Vice-President of the nonprofit CLL
Society, I will no longer have to divide my energy and will be able to focus
solely on how to improve the lives of my fellow CLL patients.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
2019 will be an amazing year. While many CLL issues remain
unsolved, and we at the CLL Society will be directly addressing those through
our research efforts, the biggest issue in the CLL world is not what should be
done, but getting the message out to all the patients and their doctors about
what are now proven to be the best treatments.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
The problem is getting out the good news.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
We have always said, “Smart Patients Get Smart Care.”™<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
We are now adding, “No Patient Left Behind.”<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
I will miss the one-on-one caring that has so defined me,
but I hope to make an even bigger difference by improving the lives of all
those who are touched by CLL.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Stay strong. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
We are all in this together.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
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Brian Koffman<o:p></o:p></div>
<div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-14025237980673220082018-11-29T11:04:00.001-08:002018-11-29T11:04:14.033-08:00Off to ASH 2018Swamped so this will be quick, but I haven't forgotten the blog.<br />
<br />
I am off to ASH 2018 where we are busy from 7 AM to 10 PM most days.<br />
<br />
I go as a:<br />
<br />
<ol>
<li>Doctor to help my CLL patients</li>
<li>Patient to help myself</li>
<li>Reporter to bring the latest news</li>
<li>Researcher presenting the largest ever survey of CLL patients to 30,000 hematologists</li>
<li>Interviewer with all the top CLL investigators and friends from the nonprofit world</li>
<li>Advocate to push for the right research and share the patient voice</li>
<li>Interviewee as I am on camera myself several times answering questions about my journey an my research</li>
<li>CMO of the nonprofit CLL Society looking for partnerships and support to keep our good work going</li>
<li>Winner of one of the CURE 2018 CLL Heroes Award</li>
<li>Friend catching up with so many of my pals from the CLL and blood cancer world of research, and advocacy</li>
</ol>
<div>
Much more during after to report</div>
<div>
<br /></div>
<div>
Check out CLLSociety.org for the updates</div>
<div>
<br /></div>
<div>
Stay strong.</div>
<div>
<br /></div>
<div>
We are all in this together</div>
<div>
<br /></div>
<div>
Brian</div>
<div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-40140719209657554252018-08-19T00:11:00.001-07:002018-08-19T00:11:06.873-07:00ASH 2017: Dr. Thomas Kipps on the ROR1 Antibody, Cirmtuzumab <div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
At ASH 2017 held in December in Atlanta, <a href="https://profiles.ucsd.edu/thomas.kipps" style="color: #52adad; margin: 0px; padding: 0px;">Dr. Thomas Kipps</a> from the Moore Cancer Center at UCSD in San Diego, CA talked about an exciting new target for very specifically killing off chronic lymphocytic leukemia cells while sparing normal cells, including normal B lymphocytes.</div>
<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
Dr. Kipps is one of the leading CLL researcher and has pioneered the work on a new antibody, cirmtuzumab that targets ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1).</div>
<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
Because ROR1 is found nearly exclusively on cancer cells, an antibody against it may be the holy grail of antibodies, one that hits only the cancer cells with few off target effects.</div>
<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
Take Aways:</div>
<ul style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; list-style-image: initial; list-style-position: initial; margin: 0px 0px 20px 20px; padding: 0px;">
<li style="margin: 0px; padding: 0px;">ROR1 is an embryonic protein that may help the embryo develop new distant organs.</li>
<li style="margin: 0px; padding: 0px;">By birth it has largely disappeared from normal cells, but it can be found on the surface of many cancer cells including CLL cells.</li>
<li style="margin: 0px; padding: 0px;">ROR1 is involved in keeping CLL cells alive even when their B-cell receptor (BCR) is blocked by drugs such as ibrutinib.</li>
<li style="margin: 0px; padding: 0px;">Cirmtuzumab is an antibody against ROR1 that it very specific in hitting just that target.</li>
<li style="margin: 0px; padding: 0px;">Early studies used extremely low doses and it was only given four times.</li>
<li style="margin: 0px; padding: 0px;">Cirmtuzumab has proven to be safe in this phase 1 trial with no serious side effects including no significant infusion reactions.</li>
<li style="margin: 0px; padding: 0px;">The ROR1 antibody has a long half-life of 21 days.</li>
<li style="margin: 0px; padding: 0px;">While the early trial was for safety, there was clear evidence of efficacy in the few relapsed and refractory patients who received the higher doses of 1 mg per kilogram with a median progression free survival (PFS) of 259 days using that suboptimal dose.</li>
<li style="margin: 0px; padding: 0px;">The combination with ibrutinib appears to be result in higher kills rates of the chronic lymphocytic leukemia cells by blocking two separate signaling pathways necessary to keep the cells alive.</li>
<li style="margin: 0px; padding: 0px;">There are ongoing clinical trials looking at the combination of cirmtuzumab and ibrutinib. Here is a link:<div class="solo_record" style="line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
<a href="https://clinicaltrials.gov/ct2/show/NCT03420183" style="color: #52adad; margin: 0px; padding: 0px;">A Study of Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies</a></div>
</li>
<li style="margin: 0px; padding: 0px;">While adding antibodies has historically not improved ibrutinib efficacy, cirmtuzumab is different in that it not just targeting a surface protein but is blocking a pro-survival pathway critical for CLL.</li>
<li style="margin: 0px; padding: 0px;">Cirmtuzumab also may be important in killing of cancer stem cells, which if proven, should reduce the risk of late relapses.</li>
</ul>
<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
We have many exciting treatments for chronic lymphocytic leukemia, but cure is still elusive. It is still very early in the story, but he can sense Dr. Kipps’ excitement and his hope that cirmtuzumab, when used in smart combinations might be part of the mix that leads to what we all dream of, namely being able to say: <span style="font-weight: 700; margin: 0px; padding: 0px;">I used to have CLL.</span></div>
<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
Here is my interview with my doctor, Dr. Thomas Kipps from UCSD. It’s 17 minutes, but Dr. Kipps is a great teacher.</div>
<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
<iframe allow="autoplay; encrypted-media" allowfullscreen="" frameborder="0" height="675" src="https://www.youtube.com/embed/E5IGVnTbvBo?feature=oembed" style="margin: 0px; max-width: 100%; padding: 0px;" width="1200"></iframe></div>
<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
Here is a link to the referenced ASH abstract: <a href="http://www.bloodjournal.org/content/130/Suppl_1/829" style="color: #52adad; margin: 0px; padding: 0px;">Durable and Specific Inhibition of ROR1 Signaling Associates with Prolonged Progression Free Survival in Patients with Chronic Lymphocytic Leukemia Treated with Cirmtuzumab</a></div>
<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
For more of ROR1 and cancer stem cells, see <a href="https://cllsociety.org/2015/05/ash-2014-dr-kipps-dr-thomas-kipps-discusses-ror1-cll-clinical-trial-and-research-on-cancer-stem-cells/" style="color: #52adad; margin: 0px; padding: 0px;">this prior interview from ASH 2014</a> with Dr. Kipps.</div>
<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
Thanks for reading.</div>
<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
Stay strong.</div>
<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
We are all in this together</div>
<div style="font-family: Roboto, Helvetica, Arial, Verdana, sans-serif; font-size: 14px; line-height: 19.600000381469727px; margin-bottom: 20px; padding: 0px;">
Brian</div>
<div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-3092663053012343442018-08-10T22:06:00.003-07:002018-08-10T22:08:10.586-07:00ASH 2017: Dr. Adrian Wiestner on Resistance Mechanism in CLL (chronic lymphocytic leukemia)I had the opportunity to interview <a href="https://irp.nih.gov/pi/adrian-wiestner">Dr. Adrian Wiestner from the National Institutes of Health</a> at ASH 2017 in Atlanta GA about his and other researchers work on how CLL cells become resistant to ibrutinib and venetoclax.<br />
<br />
Take Away Points:<br />
<ul>
<li>Ibrutinib works so well in chronic lymphocytic leukemia because it blocks the B-cell receptors (BCR) by binding to Bruton’s Tyrosine Kinase (BTK). This blocking of the BCR leads to cell death.</li>
<li>About 7-8 out of 10 patients who become resistant to ibrutinib develop a mutation C481 that prevents it from it binding and thus fully blocking BCR, allowing the CLL to progress.</li>
<li>PCLƔ2 mutation is another cause of resistance as it turns back on the BCR pathway and gives a lifeline back to the chronic lymphocytic leukemia cells.</li>
<li>Cells with the PCLƔ2 mutation tends to grow more slowly and the CLL tends to clinically progress more slowly.</li>
<li>Notch1 mutation can be associated with early progression on ibrutinib which is often not CLL but instead Richter’s Transformation that carries a poor prognosis.</li>
<li>Many patients do well on ibrutinib who have a Notch1 mutation.</li>
<li>Richter’s is rare after the first year on ibrutinib suggesting that blocking B-cell signaling may block the stimulation that leads to Richter’s</li>
<li>Less is known about the mechanism of venetoclax resistance, but upregulation of MCL-1 might play a role.</li>
</ul>
Conclusion:<br />
<br />
While the numbers are small, we are starting to better understand the mechanisms of resistance for some but not nearly all patients who progress on ibrutinib. Our understanding of venetoclax resistance is much less mature. As this research develops, there is reason to be optimistic that we can develop drugs to overcome the resistance.<br />
<br />
Here is my interview with Dr. Wiestner from ASH 2017 in snowy Atlanta Georgia:<br />
<br />
<div class="separator" style="clear: both; text-align: center;">
<iframe allowfullscreen="" class="YOUTUBE-iframe-video" data-thumbnail-src="https://i.ytimg.com/vi/QuS6Sp-wiD0/0.jpg" frameborder="0" height="266" src="https://www.youtube.com/embed/QuS6Sp-wiD0?feature=player_embedded" width="320"></iframe></div>
<br />
<br />
Here are links to some of the research referenced by Dr. Wiestner<br />
<br />
<ul>
<li><a href="http://www.bloodjournal.org/content/130/Suppl_1/263">Mechanisms of Venetoclax Resistance in Chronic Lymphocytic Leukemia</a></li>
<li><a href="http://www.bloodjournal.org/content/130/Suppl_1/262">Dissecting the Role of Individual Bcl-2 Members in Response and Resistance to Ibrutinib or Venetoclax in CLL</a></li>
<li><a href="http://www.bloodjournal.org/content/130/Suppl_1/261">Apoptosis Resistance and <em>NOTCH1</em> Mutations Impair Clinical Outcome in Chronic Lymphocytic Leukemia (CLL) Patients Treated with Ibrutinib</a></li>
</ul>
<br />
Here is <a href="https://cllsociety.org/2018/06/ash-2017-hallek-molecular-evolution-in-cll-and-venetoclax-resistance/">more on resistance from Dr. Furman</a> from our website.<br />
<br />
Thanks for reading.<br />
<br />
Stay strong<br />
<br />
We are all in this together.<br />
<br />
Brian Koffman<div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0tag:blogger.com,1999:blog-2741672436160438708.post-78707826628247364162018-08-05T22:01:00.002-07:002018-08-05T22:01:23.488-07:00He Did It<span data-offset-key="cg6s2-1-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">Hi,</span><br />
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<span style="color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, .SFNSText-Regular, sans-serif;"><span style="font-size: 14px; white-space: pre-wrap;"><br /></span></span><div>
<span data-offset-key="cg6s2-1-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">Stan Kurtz and his team, with help from so many of you, Did it. He swam the Catalina channel and raised his goal of over $25.000 for the CLL Society! Thanks to all who gave, but it's not too late to share in there joy. Consider a tax deductible (in the USA) got of $22, one dollar for each mile he swam in over 12 hours in the Pacific Ocean. </span><span style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">Or more. </span><span data-offset-key="cg6s2-1-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">It was an exhilarating and exhausting for Patty and me just being on the boat.</span></div>
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<span style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;"><br /></span></div>
<div>
<span data-offset-key="cg6s2-1-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">Now I need to get some sleep. </span></div>
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<span data-offset-key="cg6s2-1-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;"><br /></span></div>
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<span data-offset-key="cg6s2-1-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">Thanks </span></div>
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<br /></div>
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<span data-offset-key="cg6s2-1-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">SEE: <a href="https://www.gofundme.com/swimcatalinaforleukemia">https://www.gofundme.com/swimcatalinaforleukemia</a>. The swim was on the local TV news. This will help us to do so much more for others dealing with CLL.</span></div>
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<span data-offset-key="cg6s2-1-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;"><br /></span></div>
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<span data-offset-key="cg6s2-1-0" style="caret-color: rgb(29, 33, 41); color: #1d2129; font-family: system-ui, -apple-system, BlinkMacSystemFont, ".SFNSText-Regular", sans-serif; font-size: 14px; white-space: pre-wrap;">Lot's of pictures and videos on our and his FB page,</span></div>
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Stay strong.<br /><br />We are all in this together.<br /><br />Brian<br /><br /><a href="http://cllsociety.org/">http://cllsociety.org</a></div>
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<div class="blogger-post-footer">If you want a personal response, or just want to stay in touch, please email me at bkoffmanMD@gmail.com. I have no other way of contacting. Thanks. Stay strong. After all, we are all in this together. And please visit our website: http://cllsociety.org for the latest news and information.
Google serves cookies to analyse traffic to this site. Information about your use of our site is shared with Google for that purpose.. </div>Brian Koffmanhttp://www.blogger.com/profile/13250684684103918493noreply@blogger.com0