Dr, Bill Wierda on the Importance of Clinical Trials in CLL

I’m home from the European Hematology Association Congress in Copenhagen. 

I received very positive feedback on my lecture and the preliminary data from our Reader Poll with many requests for more information. We plan to follow up with another survey, Seems the 1000 plus hematologists to whom I presented the data and the folks from industry really want to know what we patients think and want.

I attended several lectures on CLL, reviewed dozens of abstracts, and had some great interviews with world experts that I look forward to sharing with you in the near future. 

After the last long day, I finally got out of the convention center long enough to walk along the harbor and see the famous The Little Mermaid statue.

This week in the Clinical Trials/The Basics section of our website we’ve posted an interview with Dr. Bill Wierda of MDACC where we talked about the value of clinical trials and how he approaches the discussion with patients about joining a clinical trial. You can read a summary of our discussion and watch my interview with Dr. Wierda here. http://cllsociety.org/2016/06/dr-william-wierda-clinical-trials-cll-chronic-lymphocytic-leukemia/

In the meantime….

Stay strong.

We are all in this together.

Brian Koffman, MD

Volunteer Medical Director of the CLL Society

http://cllsociety.org

Interview with Dr. Kipps on CLL(chronic lymphocytic leukemia) research from ASH 2015

Well, my bags are finally packed. Better be! I am at the airport ready to go to the European Hematology Association meeting in Copenhagen. 

Before the meeting starts on Thursday, I’ll be presenting some preliminary data from our Reader Poll at a symposium on Wednesday and attending a couple of other meetings with global Lymphoma groups. I have numerous other meetings and interviews set up and I’m hoping to get a little bit of time outside the convention center to at least see The Little Mermaid statue.

This week in the Conference Coverage section of the CLL Society website, we’ve posted a rambling interview with Dr. Thomas Kipps from ASH 2015. We discussed the latest data in the fight to defeat CLL using signal blockers, Venetoclax, ROR1 antibodies as well as the importance of more research. You can read a summary of our discussion and watch my interview with Dr. Kipps here. http://cllsociety.org/2016/06/dr-kipps-signal-blockers-venetoclax-ror1-antibodies-importance-research/  ‎

From time to time, we will make you aware of in-person meetings coming up for those of us affected by CLL. In June, they include:

June 16^th at 6 PM in Salt Lake City, UT: The Lymphoma Research Foundation will be hosting Updates on Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma as part of their Ask the Doctor series. You can find out more information and register here. http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=9384957 

There is no charge to attend.

In the meantime….

Stay strong.

We are all in this together.

Brian Koffman, MD

Volunteer Medical Director of the CLL Society

http://cllsociety.org

Venetoclax in refractory CLL (chronic lymphocytic leukemia) patients with deletion 17p And News about Upcoming Support and Education Opportunities

Friends,

This week in the 2015 Conference Coverage section of the CLLSociety.org we have posted my final interview with Dr. Stephan Stilgenbauer while we were at the American Society of Hematology (ASH) annual meeting in December 2015 in Orlando. We discussed his late breaking abstract on venetoclax in refractory CLL patients with deletion 17p. You can see a summary and view our interview here. [http://cllsociety.org/2016/03/ash-2015-dr-stephan-stilgenbauer-dramatic-responses-venetoclax-relapsed-refractory-rr-17p-deleted-cll/]

Last Saturday, it was my privilege to speak at The Southern California Blood Cancer Conference sponsored by the Leukemia and Lymphoma Society in Anaheim, California on being your own advocate. The CLL Society team was in attendance at our booth and it was great to meet all of you who were there. It was a super meeting.

Our first satellite support and education group launched yesterday at City of Hope, Duarte CA and I believe the 15 patients and caregivers shared and learned together. We will be meeting the third Monday of each month at 7 PM of every month. For more information, view the flyer. [http://www.cllsociety.org/docs/cohmarch2016.pdf] There is no charge to attend.

We are also forming a new patient and caregiver support meeting in Charlotte, NC. If you are interested, please complete the online survey to indicate your preferences for days and times. [https://charlottegroup.questionpro.com/] We look forward to getting started. 

There is another educational meeting coming up, this time by LRF.

April 2^nd at 7:30 AM: The Lymphoma Workshop: Understanding Lymphoma Basics and Current Treatment Options hosted by the Lymphoma Research Foundation will be held in Manhattan Beach, California. It will be held at the Manhattan Beach Marriott from 7:30 AM to 3:30 PM. You can find out more information and register here. [http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=9357081#location] There is no charge to attend.

In the meantime….

Stay strong.

We are all in this together.

Brian Koffman

Volunteer Medical Director of the CLL Society

ASH 2015: Dr. John M Pagel on Idelalisib as Frontline Therapy in CLL (chronic lymphocytic leukemia)

We have just learned of the good news of the broad FDA approval in the USA of ibrutinib in the frontline setting for CLL.  

This step forward in CLL therapy only comes after years of research and is due in no small part to the brave patients who volunteered for these trials including the pivotal RESONATE-2 trial.

As a reminder, ibrutinib is a small molecule taken orally, a tyrosine kinase inhibitor or TKI, that inhibits the BTK pathway that is so important for  B cell communication. By doing so, it blocks a critical pro-survival signal in our CLL cells and helps control our disease. 

I will comment more on the significance of this frontline approval in a coming post, but to give some perspective, I want to reflect on the only other approved oral TKI for CLL, namely idelalisib that inhibits the PI3Kδ pathway. This pathway is also important for B-cell signaling in our CLL cells and blocking it also blocks the same strong survival signal. That is a big part of the reason why both these drugs work as well as they do. 

Researchers want to discover which CLL patient will get the most benefits with the least risks from these new therapies.

At ASH 2015 in December, many researcher were initially surprised by the amount of toxicity discovered when idelalisib was studied frontline or in the treatment-naive CLL population. 

Keep in mind that it is currently only approved for use in combination with rituximab in the relapsed and refractory CLL population, not frontline. This trial was to look at its safety and efficacy in this new setting.

I interviewed Dr. John Pagel of Swedish Hospital in Seattle, WA on the importance of this negative findings.  

It is a truism in science that we often learn as much or more from the trials that don't go as planned as from those that do.

Though most of the research on idelalisib presented at the ASH meeting was positive, the title of this abstract tells us there were significant issues:  Idelalisib Given Front-Line for the Treatment of Chronic Lymphocytic Leukemia Results in Frequent and Severe Immune-Mediated Toxicities.

Three quarters of the patients had grade 3 toxicities or severe problems. For 56% of them this was liver toxicities where the blood tests that measure liver inflammation were 5 to 10 times the upper limit of normal. These are much higher levels than generally seen when idelalisib is used in patients who have had prior treatments.

The good news is that with immune suppressive therapies including steroids, all the patients recovered.

The details of the trial are here.

Why then when ibrutinib is relatively benign in the frontline setting, did a somewhat similar drug have such unexpected problems.

Any drug may have effects on cells that are not their therapeutic target, resulting in unwanted side effects. One theory is that idelalisib lowered the balancing activity of the regulatory T cells or Tregs that are important in preventing auto-immunity. The PI3Kδ pathway is critical to the function not just of CLL cells but of the Tregs too. 

This is why we need to do research. This is why we need to laud the brave subjects who jump into these trials. Without them, we make no progress.

Here is my interview with Dr. Pagel on this subject from ASH 2015.



As Dr. Pagel emphasizes, idelasilib is a powerful drug that helps many patients with CLL. How and when to best use it is a matter of ongoing research.

Stay strong

Brian

ASH 2015: Dr. Stephan Stilgenbauer on clonal evolution in CLL (chronic lymphocytic leukemia) and update on many upcoming meetings

This week in the 2015 Conference Coverage section of the CLL Society website, we have posted an interview with Dr. Stephan Stilgenbauer as he discusses clonal evolution at the American Society of Hematology annual meeting in December 2015 in Orlando. You can see a summary and view his interview here.

Last week was very busy as I attended the CLL Research Consortium meeting from Wednesday through Friday and then took a redeye flight to Atlanta for a CLL educational meeting on Saturday. I spoke to the 30 attendees, and was thrilled that almost 90% of them already knew of the efforts we have been making with the CLL Society.

There are more meetings coming up for those of us affected by CLL:

March 12th at 7:30 AM in Scottsdale, AZ: The Lymphoma Workshop: Understanding Lymphoma Basics and Current Treatment Options will be hosted by the Lymphoma Research Foundation. You can find out more information and register here. There is no charge to attend.

March 17th at 6 PM in Chicago, IL: The Lymphoma Research Foundation will be hosting Updates on Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma as part of their Ask the Doctor series. You can find out more information and register here.  There is no charge to attend.

March 19th at 8 AM: The Southern California Blood Cancer Conference sponsored by the Leukemia and Lymphoma Society will be held at the Anaheim Marriott. You can find more information and register here. The CLL Society will have an exhibit table at the conference. We look forward to seeing you there. There is no charge to attend.

March 21st at 7 PM: First CLL Society Support and Education Network Patient Support and Education Meeting will be held at City of Hope: For those of you in the Los Angeles area, a new patient support and education group is forming. For more information, view the flyer. [http://www.cllsociety.org/docs/cohmarch2016.pdf] There is no charge to attend.

March 22nd at 6 PM in Atlanta, GA: The Lymphoma Research Foundation will be hosting Updates on Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma as part of their Ask the Doctor series. You can find out more information and register here. There is no charge to attend.

April 2nd at 7:30 AM: The Lymphoma Workshop: Understanding Lymphoma Basics and Current Treatment Options hosted by the Lymphoma Research Foundation will be held in Manhattan Beach, California. It will be held at the Manhattan Beach Marriott from 7:30 AM to 3:30 PM. You can find out more information and register here. The CLL Society will have an exhibit table at the conference. We look forward to seeing you there. There is no charge to attend.

In the meantime….

Stay strong.

We are all in this together.

Brian Koffman, MD
Volunteer Medical Director of the CLL Society

http://cllsociety.org
http://bkoffman.blogspot.com

CLL PATIENT AND CAREGIVER EDUCATIONAL FORUM at City of Hope this Saturday

I'll be at City of Hope this Saturday with the latest news from ASH earlier this week and learn how a support group can improve our odds. It's not to late to register at http://cllsociety.org/docs/COH%20Patient%20Meeting.pdf

CLL PATIENT AND CAREGIVER EDUCATIONAL FORUM

In partnership with the City of Hope and the Leukemia and Lymphoma Society (LLS), the CLL Society invites you to attend a CLL patient education forum and the launch of a Los Angeles-based local support group sponsored by the CLL Society Support Network.
Date: Saturday, December 12, 2015 

• 8:30 AM – 9:00 AM Registration
• 9:00 AM – 12:25 PM Program

Location:
Platt 3 Conference Room City of Hope 1500 East Duarte Road, Duarte, CA 91010
AGENDA

• 9:00 AM Diagnosis and Frontline Treatment Tanya Siddiqi, MD
• 9:30 AM Relapsed Disease, Novel Therapies Steven Rosen, MD
• 10:00 AM Q&A Siddiqi, Rosen
• 10:20 AM Break
• 10:35 AM Services of City of Hope
• 10:45 AM Services of Leukemia and Lymphoma Society
• 10:55 AM Being Your Own Advocate Brian Koffman, MD
• 11:10 AM Break
• 11:25 AM Support Group Discussion

Why attend a support group, rules for running and participating in a support group, summary and plans to re-meet and option to sign up for support group meetings and training as a facilitator Terry Evans and OC Support Group Members

• 12:25 PM Conclusion

HEADING HOME FROM ASH

Our flight is delayed from Orlando and we have a tight connect in Phoenix. What else is new! Not looking good.

ASH 2015 was amazing.  So much good news and clarifying news on novel therapies.

Watch here and on the CLL Society website for the news, interviews and updates.

Here are a few teasers:

• Venetoclax (ABT-199) looks very helpful for those who have failed ibrutinib or idelalisib.
• ACP-196, a new BTK  inhibitor has stellar results with few side effects.
• Ibrutinib does a super job upfront in the over 65 gang. Should become standard of care frontline.
• The addition of idelalisib to bendamustine and rituximab (BR) greatly improves outcomes, but the use of idelalisib frontline needs to be managed more carefully to get the good results it offers due to increased risk of liver issues.
• Promising results with new signal blockers such as ONO-4059 and duvelisib and TG-1202 and the immune modulator, CC-122 and high dose methylprednisolone (HDMP) and new antibodies and much more.

More details and other results soon.

Stay strong.

Gotta get ready for our flight, I hope. The problem is a broken bathroom door.

UPDATE: After changing the flight 3 times, we would have missed our connection by about 15 minutes, so we changed everything to fly into LAX  more than an hour from home, but at least in the same time zone. Our bags are a different story.

Brian

I am off to ASH 2015 to learn everything I can about CLL and I have a miserable cold.

I got my biannual cold that seems to come just as I am planning to get on the plane to the be the only family doctor among 30,000 or so hematologists and researchers from around the world.

Despite my aches and cough and runny nose, I am looking forward to learning all that I can on CLL, absorbing it and sharing it here and on the CLL Society website.

Highlights include the first data on an ew BTK inhibitor, ACP-196 (NEWS BREAK: now officially called acalabrutinib), more on other exciting drugs in development including venetoclax (ABT-199) and several promising new signal blockers and more on SYK inhibitors and new antibodies and new combos and more on approved drugs such as ibrutinib and idelalisib and obinutuzumab and ofatumumab and more smartly focused material on chemo and on new understandings of how CLL is treated in the real world and how it might be treated soon and so much more.

Plenty of interviews scheduled with experts from around the world, many whom are old friends and some who are new to me, but have published important research.

Hundreds of great abstracts (I have reviewed about 200 so far) and many oral presentations and press conferences.

I am also meeting with other patient advocates and friends from around the world to share best practices.

I will try to share some live updates from ASH 2015 because it is so exciting, but mostly I like to digest the research over a few weeks so that it can be understood and put in meaningful perspective.

The only thing missing is lots of sleep.

So now I am going to bed. Flight tomorrow AM.

Despite my CLL, I have almost Normal Lab as I head to ASH next week

I am back from a quick trip to Ohio State University, Columbus, Ohio to see Dr. Byrd for my ibrutinib trial with good news.

My clinical exam was normal - no enlarged nodes or liver (my spleen has been long gone, removed more that 8 years ago in an unsuccessful attempt to raise my low platelets). The rest of physical exam was normal.

But what about the lab you ask- many of us with CLL may look good, but it is often our labs that are wonky.

Not mine. No anemia and basically normal platelet and normal neutrophil counts. The total lymphocyte count that includes our cancerous B cells was even a bit lower than normal.

So if my total lymphs are low, then my cancerous CLL cells must also be low. And that is very good news.

I won't know the actual number of lymphocytes that are part of my bad monoclonal clone until the fancy flow cytometry come back in a few weeks. That test tells what percent of my lymphocytes are cancerous.

And then even later, I will learn the results of the important research test that looks deeply at my cells for the common mutations that could make my cells resistant to ibrutinib. A negative test (no significant mutations) bodes well for the ibrutinib to continue to work its magic, a positive finding  suggest a relapse may be in the offing.

This is important because in high risk patients such as yours truly with an unstable cell type (17p deletion and complex karyotype) there is a small but real annual rate of relapse on ibrutinib. This test looks into the future and projects who at risk.

That's why I am always pushing for a second step beyond monotherapy with a signal blocker (ibrutinib and idelalisib). We need a one-two knock out punch.

My blood chemistries are mostly good too, though one very old school, inexpensive marker is abnormal. My LDH (Lactic DeHydrogenase) or LD has been slowly climbing.

This is a very nonspecific test as LDH is a ubiquitous enzyme found in most cells (and in bacteria too) that can be a marker of all kinds of cell destruction (heart, blood, lung, liver and even brain are common sources) or certain serious infections or certain types of tumor proliferation or nothing.

My LDH was been slowly trending up for a year and is now slightly above normal. Dr. Byrd is not worried as the much more specific markers of disease are all reassuring.

When we have CLL, there is always some fly in the ointment, some minor distraction, some nagging uncertainty.

Life rolls on and life is good. With CLL, we are never dealt royal flush, never have a sure thing, but when we have a darn good hand we need to celebrate and enjoy.

So I am off to ASH 2015, the largest and most important hematology meeting of the year, next week in Orlando. I am fighting a cold and tenosynovitis of my right thumb (think pain with using your thumb), but I am not going to let such trivialities slow me down, though I am going to take a short nap as soon as this post is online. Sleep- sweet nature's balm.

ASH will be crazy for sure because as it will be nonstop interviews and meeting and abstracts and press conferences.

I go wearing at least 5 different hats:

1. A patient who want to know the latest about CLL as I am not cured
2. An advocate pushing to get better trial design and better access to the best possible therapies
3. A reporter bringing the latest news from the 100s of abstracts and oral presentations, press conferences and interviews with the experts
4. The medical director of a nonprofit corporation meeting with other nonprofits and industry to find ways to mutually support our efforts to get the word out and help patients
5. A doctor who directly helps care for patients with CLL (with the heavy lifting being done by their hematologists)

Someday soon I also hope go as a researcher or as a speaker as I did at iwCLL where I spoke on how to improve access to expensive drugs in front of 500 plus doctors. That will take more work and effort, but I have plans.

I also am getting used to the tables being turned and having the microphone in my face as I am now the occasional interviewee and not the interviewer.

And I go as friend. After so many years and conferences, many of the top CLL researchers have become friends, members of our scientific advisory board and active in our nonprofit CLL Society.

There is not too big number of patients and advocates in attendance, but I will connect with some of them there and at a related meeting for nonprofits in the blood cancer world that we will attend.

Much to share. All good.

Sign up for the CLL Society alerts here. It is where I am doing most of my writing these days and the alerts are the best way to keep up to date. We have been putting up new posts almost twice a week, so   it is the place for the latest CLL news. And our next newsletter will be out before the year's end

Finally, if you live in the LA area, please join us at City of Hope on Dec. 15 for a patient education forum and the possible launch of a new support group. Details are here.

Stay strong.

We are all in this together.