ESH 2014: The Future Role of FCR and new data on venetoclax and rituximab in CLL (chronic lymphocytic leukemia) and my latest lab results

I thought I sneak in one last post from LAX before I board my plane to Wroclaw, Poland via Munich.

It is mostly about the new posts on the CLL Society's website and our nonprofit's news, but I wanted to share that my latest lab results from my visit to the infusion center for IVIG remains most boring with a low normal hemoglobin, a high normal platelet count and an absolute lymphocyte count of 1.2.  YEAH! Of course that really matters is the count of clonal B cells and that takes flow cytometry, but at least I know that nothing major is happening. Slow and steady makes me happy.

This week on the CLL Society website we bring the second part of our interview with Professor Michael Hallek of Koln, Germany, the director of the German CLL Study Group and a major CLL researcher and thinker.

He starts by discussing his “fast boat” adaptive trial strategy (similar in many ways to that of Prof. Hillmen in the UK), essentially looking for the most tailored therapy based on not just predictive factors, but also on how we patients actually respond in trials. He is looking for what I call that perfect Goldilocks’ mix of “ as much as necessary, as little as possible” therapy.

In the second half of the interview, he makes a cogent argument for the ongoing use of FCR frontline in select patients. While many of us are not fans of chemo-immunotherapy (CIT), Professor Hallek has strong data to support his perspective. Listen with an open mind.

Please give a look here in our section on conference coverage from 2014.

We also share my comments and background on an important oral abstract presented at the 20^th Congress of the European Hematology Association (EHA), June 11-15, 2015 on venetoclax (ABT-199 or GDC-199) and rituximab. In relapsed patients, the total response rate, the complete response rate, the MRD- rate and the ability for some to be able to remain disease free after stopping the drug is important data that you can find here in our 2015 conference coverage section.

We have a significant backlog of important educational material mostly from large conferences such as ASH 2014 and others from 2015 that we plan to post over the next few months.

In a first step to speed up the process, our first high school intern volunteer, the granddaughter of the CLL Society's attorney, has joined us online to help her earn her community service hours by helping us catalog all the videos that we have produced and are storing on the web.

We are working hard to expand what we offer to the tens of thousands of online readers and to actuate our ambitious plans for patient-centric, physician-curated live education and support. One volunteer medical director (yours truly), his unpaid wife and one part-time RN can’t do it all, although I have to say we have made some amazing progress in our mission to meet the unmet needs of the CLL community in the less than 90 days since our nonprofit’s website launched. Our website is #1 in organic Google searches for CLL Society despite having no search engine optimization in place. We are too busy trying to get our content up.

There is so much more we must do. Your suggestions, help, support, donations, ideas, and feedback are what guide us and keep us going.

We remain forever committed to open content for all with no need to sign in or share any of your personal information to see a video or to get the help you need. If you haven’t done so already, we encourage you to please sign up to receive alerts regarding new postings and for our quarterly newsletters (first one will be published in September) and to share with other patients, caregivers or concerned family or anyone whose life is touched by CLL.

The CLL Society will be at iwCLL in Australia in September to cover the news and we are planning an amazing patient meeting the day before the researchers' meeting in Sydney with Lymphoma Australia. 

Stay strong.

We are all in this together.

Brian Koffman

Volunteer Medical Director, CLL Society

Frontline therapies In CLL (Chronic Lymphocytic Leukemia)

In this lively ONCLIVE multi-part series of polite debates among four world class CLL experts (Drs. Byrd, Furman, Ma, and Kipps), I was struck by the conservative approach of the panelists to frontline therapy.

Almost all the discussion in this 13 minute segment is about chemo-immunotherapy (CIT).

Keep on mind that except for patients with 17p deletion where ibrutinib is approved, chemo-immunotherapy is all that is approved for frontline therapy. That said, we all know that many doctors including several on this panel would discuss with their patients other frontline options besides those they discuss on camera, namely FCR (fludarabine, cyclophosphamide and rituximab) or BR (bendamustine-rituximab) or chlorambucil and obinutuzumab.

Dr. Kipps points out the potential advantages of the chlorambucil and obinutuzumab in elderly patients with a less resilient bone marrow. This relatively gentle approach has achieved a 20% complete response rate and a 26.7 month mean progession free survival, much better than the other arms in the trial that lead to its approval. For the details of the study published in the NEJM please click on this link.

Drs. Byrd and Kipps talk glowingly about the very long term benefits of FCR in a small subset of patients with the best prognostic markers: mutated with no other bad prognostic indicators. This is a subject we have visited frequently visited in the past. Here Professor Hallek and I discussed this topic in this post in the context of the role of chemo-immunotherapy (CIT) way back at iwCLL 2013. I am still waiting for the published material on that low risk subgroup that is looking more and more as if they might be CURED!

In this ONCLIVE video, there is also debate on the need to complete all the cycles of FCR to get the full benefit. I fully agree with Dr. Kipps that the evidence suggests getting to MRD (minimal residual disease) negativity is what determines our prognosis and not the number of cycles it takes to get there. I quote from a Blood editorial by Sebastian Böttcher on the original research: "current investigation suggests that the number of treatment cycles also becomes irrelevant as long as MRD negativity can be attained." 
The full text of the original research is accessible here. The authors state in the abstract that:" MRD-negative patients had comparable PFS ( progression free survival) and OS (overall survival), independent of the number of courses received or interim staging. Early MRD eradication may be a desirable goal, prompting consideration of early discontinuation of treatment."

Dr. Furman hastened to point out the potential downside of chemo-immunotherapy and also that the group that did so well is a group that should do well with any therapy.

In this article from the British Journal of Hematology, we learn: "patients treated with purine nucleoside analogues (PNA) had a significantly increased risk of subsequent second LPD (5·2%) compared with patients who had not received PNA (1·9%; P = 0·008)"  PNA are drugs such as fludarabine and LPD are lymphoid cancers.  In fact, they go to stated that the only factor found to be associated with an increased risk of a secondary lymphoma for those us with CLL was prior treatment with chemotherapy.

That certainly does give one pause.

There is also some very interesting comparison of BR versus FCR, a subject that we extensively reviewed in this prior blog post with Dr. Jeff Sharman.  I appreciate Dr. Kipps' careful analysis of the different arms of the trial to ensure that we are really comparing apples to apples.

Give a listen and please share your comments.

Again, thank you ONCLIVE for bringing us this great panel discussion.

ESH 2014: Prof. Stephan Stilgenbauer Discusses Prognostic Factors, FCR and Implications for Therapy in CLL (chronic lymphocytic leukemia)

In part two of my interview from ESH in November 2014 from Greece with Professor Stilgenbauer of the University of Ulm, Germany we go deeper on the topics we cover in part one and introduce new subjects. I recommend you take a look at that post if you haven't already. That prior post also has links to even earlier reviews of some of the same areas of discussion.

In this segment, the doctor starts by using the examples of 11q or 17p deletion that help explains some of the subtleties of the difference between prognostic and predictive factors.

It is a nuanced subject, but one worthy of our efforts to understand as it can help guide our therapeutic choices.  His examples clearly outline the differences. Hopefully my brief introductory notes that follow also help.

The best known bad player found by FISH or interphase fluorescence in situ hybridization is deletion of 17p.

When the short arm of the 17th chromosome (17p) is deleted, gone with it is TP53 that is important in maintaining genomic stability when our DNA is reproducing itself. Because of its critical role in guarding the fidelity of each copy of the genome when our cells are replicating, it is considered a tumor suppressor. The doctor explains how it also fosters resistance to most chemo-immunotherapies.

The number two bad boy is 11q deletion.

The 11q arm carries ATM that is also involved, those less critically, in the same pathway protecting the stability of our genome. But the new discovery is that 11q deletion may also lead to loss of BIRC3 that leads to the jamming on of the pro-survival and anti-apoptotic NF-κB signaling pathway. More on this in later posts.

It's complicated, but the pieces are coming together.

Dr. Stilgenbauer points out that in those of us with 17p deletion with the relatively good news of having a positive mutation status, our CLL may be slow to progress. This combination of + mutation status and 17p deletion is an example of a prognostic factor- prognosticating about how we will do in the future.

He next points out that when patients with that same combo eventually do need treatment, it will most likely not respond to conventional chemo-immunotherapy (CIT) such as FCR. This is an example of a predictive factor, representing a "prediction" of the likelihood of a given therapy working.

If we are both unmutated and 17p deleted, sadly odds are we will both progress quickly and do poorly with traditional therapies. A double whammy. Bad prognostic and predictive factors. That's me.

He correctly points out the good initial response rates to CIT for those with 11q deletion (I am in this group too), but he neglects to point out that while we might get a deep response, it is not durable, possibly due to our cancer's ability to mutate more freely. He is right in highlighting the strong correlation between unmutated status and 11q deletion, which raises the questions about which is these two gives us the bad prognostic.

The professor's take on the possible "cures" with FCR is also instructive. Please give a critical listen.Much to ponder.

We also talk about the need for deep sequencing to search for 17p deletion or to check for TP53 function. He explains the new versus old ways to look at the chromosome.

Dr. Stilgenbauer outlines the sinister consequences that happens when the selective pressure of CIT is applied to even the smallest subclone population of 17p deletion cells. They can rise up and take charge when the cancer returns.

I believe that FISH is important but only a first step. Today we need to look for both deletions missed by FISH and smaller but critical subclones that are beyond the resolution of FISH. CLL management needs to move in this direction.

I don't want this post to be too much of a downer. While all statistics and cellular biology are important for predicting what happens to different groups, they do not determine individual destiny. And many of the new therapies' responses are blissfully blind to FISH status. I myself am unmutated, 11q deleted, 17p deleted, ZAP 70+, CD38+, have a complex karyotype and I am doing fine, thank you, but knowing this helped informed my decisions.

He closes with the familiar clarion call of the twin needs of having a CLL expert on our team and for more research.



More from ESH, Greece coming soon, including Dr. Wu on clonal heterogeneity and Dr. David Porter of U. Penn on CAR-T in CLL.

Many interviews to share from ASH last month in San Francisco are on the way.

Stay strong. We are all in this together.

ASH 2014: Interview with Dr. Susan O'Brien and Dr. Bruce Cheson on CLL (chronic lymphocytic leukemia)

There is much to report from ASH 2014, and this sweet interview from Medscape offers a short synopsis of some of the highlights.

Over the coming weeks I plan to fill in the details with more comments and videos, but this is a nice and succinct place to start.

There are some priceless moments, thanks to the wise and dry humor of Dr. Cheson and the honest and patient centric attitude of Dr. O'Brien.

First, right up front, I really appreciate that Dr. Cheson points out just how out of date are even the most recent CLL guidelines that were developed only a few years ago.

Are you listening, community oncologists? The published CLL guidelines are out of date.

I am glad he also asked about the secondary malignancies with chemo-immunotherapy, a question too often swept under the carpet in many presentation on CLL treatment. We know there is a small but real risk of MDS or myelodysplastic syndrome (for an explanation of the relationship of MDS and CLL from Dr. Steensma, click here), a difficult to treat form of cancer that presents as bone marrow failure, that may come along as a late and serious complication with FCR (fludarabine, cyclophosphamide, and rituximab), but we don't have much data yet on the risk with BR (bendamustine and rituximab).  Because bendamustine is a DNA damaging alkylating agent similar to chlorambucil (Leukeran) and cyclophosphamide (the C in FCR), it is likely that MDS will also present as a late, but hopefully infrequent ugly complication after BR.

What we do know already is that now that we are living longer with our CLL, we are getting more secondary cancers (click here for a reminder of our risks), especially blood cancers.

Don't miss Dr. Cheson's hand gesture when Dr. O'Brien talks about the minority of patients that do so very well on FCR, a topic that we have visited here more than once (click here to hear Dr. Hallek at  iwCLL discuss who gets the most benefit from FCR).

Another highlight comes right after the honest discussion of the follow up important trial of the two old school chemo-immunotherapies that are duking it out for supremacy in the CLL world, namely the  FCR versus BR (for more on this trial from Dr. Sharman click here). After Dr. O'Brien's honest and upbeat response, Dr. Cheson asks her, quite properly in this era of new treatment options: Do we care?

Yet another interesting moment occurs when he asks Dr. O'Brien to choose between ibrutinib, idelalisib, and ABT-199: If they were all available: Which one would you pick?

She refuses to answer.

Their discussion on the meaning of minimal residual disease or MRD negativity in the era of novel therapies is both informative about what we know but even more so about what we don't know.

Only time and trials will help sort al this out.

Dr. O'Brien has her own hand gesture when she describes just how much above 50% was the progression free survival curve for ABT-199 at 18 months. We need more data. And more time to sort this all out.

I wish I had produced this video. I don't usually see the role of my blog to share what is already available on other websites, but this is good stuff and there was much in it that cried out for commentary and context. I wanted everyone who reads my blog to have the link with it here.

Please enjoy this Medscape Interview:

CLL: It's the Best -- and Most Confusing -- of Times

Thanks for your help and support.

                                          

ASCO 2014: Dr. O'Brien Discusses Improved Trial Designs, CT Scans and the role of Chemo-immunotherapy In Frontline Therapy in CLL (chronic lymphocytic leukemia)

I am back from ASH 2014 with some informative video interviews from Drs. Hillmen, Byrd, Burger, Wiestner, Kipps. Sharman, Roberts, Pagel, and Kay. The congress was a huge success and I will be reporting on the important abstracts and news over the next few months first here and then on our new website for the CLL Society Inc.

I also am very excited with the video interviews from ESH in Greece including ones with Furman, Porter, Hallek, Stilgenbauer, Wu, and Brown.

But first I have to share this fourth and final thoughtful audio interview with Dr. Susan O'Brien despite all its hisses and pops.

We pick up on the issue of ethical trial design from the third part of her interview on the issue of equipoise. If you missed part 3 or part 1 or 2, please enjoy by clicking on the numbers.

In this segment, Dr. O'Brien and I discuss the place of CT scans in clinical trials and in the real world of CLL therapy. Her answer is not black or white but is balanced and well considered.

Next Dr. O' Brien gives as a nuanced response to the question of what might be the possible role for chemo-immunotherapy in and out of trials.

Spoiler alert: Consider FCR frontline if you are young, healthy, mutated, and trisomy 12. But only under those circumstances>

 Here is Dr. O'Brien



More soon from ASH and ESH.

And thanks to the well over 300 of you that have completed our survey. If you haven't done it yet, please, take a few minutes to add your voice to the others as to what are your particular unmet needs in living with CLL. We are building the nonprofit CLL Society Inc. in response to those needs.

We will be taking the survey offline in one week on December 19, so please don't delay.

Here's the link.

And a very special thanks to those of you who have generously given a tax deductible donation to help us with our website construction and developing our CLL specific support groups.

More details to follow soon after we have analyzed the survey results.

We still are welcoming any contribution, large or small. At the suggestion of several of you, we have added a donate button at the top of the blog and on our placeholder website for the CLL Society Inc.

Thanks for all your help.

We are all in this together.

                                           

ASH 2013: Dr. Claire Dearden Discusses CLL Treatment in the Elderly

One of the nicest doctors in the world of CLL is the English hematologist or should I say haemotologist, Dr. Claire Dearden of the Royal Marsden in London.

At ASH 2013, Dr. Dearden and I reviewed the new studies on the treatment of the most common group in CLL but the most underrepresented in clinical research, namely the elderly patients.

At ASH 2013, several papers made significant progress addressing this gap and that is what we discussed.

We can hear echoes of my discussions with Dr. Jeff Sharman in a recent post on the trial of idelalisib with and without rituximab. In that interview, we focused on the ethics of that placebo controlled trial.

We may also recall that Dr. Jennifer Brown and I discussed in another ASH 2013 post the very exciting trial of chlorambucil alone, with rituximab or with obinutuzumab that Dr. Dearden mentioned.

There was also important information of relevance for this population group in the long awaited study comparing FCR versus BR. For another thoughtful discussion on this, check out Dr. Jeff Sharman's excellent blog post. Here is a link to the actual study data presented at ASH. In the over 65 group, there was no progression free survival (PFS) advantage for FCR over BR despite the former's greater toxicity, especially in this age group. This is news we can use.

But before we get started in deconstructing the data, one of the first issues we must address is exactly how to define old. Turns out there is much research on looking at the biological versus chronological age. The CIRS scale is commonly used to look at co-morbidities, but as Tait Shanafelt out of Mayo Clinic pointed out in his important educational paper at ASH on this topic, we need to look at quality of life, life expectancy (approximately 20 years for those us 65 years old), and frailty. It's not just calendar years.

This is the biggest reason I push for a healthy lifestyle. It is not that a plant based diet and regular exercise will cure our cancer, but we are sure to do better if we have fewer co-morbidities, and living healthy helps with that. We don't need to add diabetes or renal disease or heart trouble to our list of woes that come pre-packaged with CLL. More problems unrelated to CLL lead to more problems related to the CLL.

Here is the interview with Dr. Dearden.


The news is good. Options are improving. I am not thrilled with chlorambucil as the backbone of the therapy, an admittedly gentler but still old school alkylating agent in the same class as bendamustine or cyclophosphamide (cytoxan or the C in FCR) or mustard gas. Just because it's a pill, doesn't mean that it's safe. Moreover, I am sure that the heavy lifting in this trial was done by the immunotherapy agents, rituximab and especially obinutuzumab. But chlorambucil is cheap (as little as $1.50 a day for the lowest dose) and easy to take.  It is very popular in Europe and was a favorite of the late great Dr. Hamblin.

One more point.

As we hear from the end of our discussion, the choices are complex and nuanced. As I have said before and as has been proven in a study out of Mayo, we do better with a CLL expert as part of our team guiding us through our therapeutic decisions.

Finally, Dr. Dearden reminds us of the many unanswered questions and that's why we need more research.

I have been traveling and meeting with fellow CLL friends, but I am back and trying to catch up on a backlog of videos and personal stories and adventures to share.

Stay tuned. Posting should be more frequent over the next month.

ASH 2013: Dr. Jeff Sharman Discusses FCR versus BR in Front Line CLL

In this interview, Dr. Jeff Sharman gives us some understanding of the important trial data presented at ASH 2013 that compares FCR (fludarabine, cyclophosphamide, rituximab), the gold standard chemo-immunotherapy (CIT) to BR (bendamusine-rituximab) the new kid on the block and very popular with community oncologists.

In the excitement and promise of the new era of gentler and more effective oral medications for CLL, there is still a diminishing group of patients that for many reasons will continue to chose a chemo-immunotherapy (CIT) approach.

One possible reason is that for a few patients with excellent prognostic factors, a significant subset of those will reach MRD negativity and for that group FCR produces exceedingly durable remissions, starting to hint a possible cure. A half year of harsh but not the worst therapy, and you're done. Time to get on with your life without any daily pill reminding you that you have CLL.

Professor Hallek discusses this special group in my short interview from iwCLL last year.  I would not be completely dismissive of the value of CIT in those special circumstances.

Sadly insurance coverage and expense will be another reason that we will still see chemo. Older drugs are cheaper than newer drugs.

And even more sadly, patients' and physicians' unawareness of the rapidly changing therapeutic landscape will limit some of us CLLer's option to what our oncologist is most comfortable with it.

A few of us won't be able to tolerate the new oral therapies due to side effects, but as more options and new TKI's are approved I suspect that will be a vanishing small number. There are also the very few patients who have progressed on ibrutinib (the only oral TKI approved for CLL at this time and available by prescription) and an unfortunate group of us who both can not qualify for a trial or who have no access to the new meds because of where they live or their insurance and who need treatment NOW and can not wait for a different option.

That said, the FCR versus BR data welcomed as it is, is hardly the blockbuster news that it would have been a few years ago.

Ibrutinib and idelalisib and ABT-199 and obinutuzumab and others have rightly stolen the spotlight at ASH and elsewhere. Their time has come, and not a moment too soon.

Still CIT is not going to quietly fade away so fast so let's look at this important ASH abstract.

This link gives the data.

This link explains what is meant by the grade of adverse events and reminds us that a grade 3 adverse event is severe or disabling, a grade 4 is life threatening and a grade 5 adverse event is polite medical talk for a side effect that kills the patients. So when we see that on the FCR, we patients had a 90% of a Grade 3 or worst hematologic side effect compared to only two out of three in the BR arm.

The price of this higher that high toxicity and small but real risk of dying from FCR was an impressive 98% overall (ORR) response rate with nearly half of those being CR (complete responses). With BR the ORR is the same but the CR is 38%. MRD (minimal residual disease) negative data was not presented. Progression free survival was better for FCR in those under 65 years old, but not in the older group.

So very impressive results, but significant toxicity. This is an old and too common story with chemo: The more toxic the drug, the better it works. FCR is better in younger patients, but comes with more risks and misery.

New targeted and biological therapies break this paradigm and that is why when we have a choice, we should be putting the emerging therapies high on lists of options.

Remember too that this trial was for front line therapy in fit patients where access to the newer treatments in even more difficult.

Listen to Dr. Jeff Sharman and get his take on this important study. Dr. Sharman is a smart, very busy and compassionate guy who has done much to help the CLL and other blood cancer community and I am grateful for the time he gave for this interview at ASH 2013.



Dr. Sharman has an excellent blog himself where he covers much of the same and even more detail on the trial here.

iwCLL 2013: Prof Hallek Discusses a Focused Role of Chemo-Immunotherapy

In this brief second part of a three part interview from iwCLL 2013, Professor Hallek precisely defines the populations that do well with chemo-immunotherapy.

It is important to keep in mind that it was only with the addition of rituximab, an anti- CD20 monoclonal antibody,  to a chemo backbone of FC, comprising together the "gold standard" therapy of FRC, that a survival advantage was first shown. Prior to the German study presented at ASH only a few years ago that proved FCR prolonged lives, no therapy had been shown to help us live a day longer.

At iwCLL 2013, we learn some very important new wrinkles on exactly who it is that benefits from FRC.

There should be no debate that the role of CIT (chemo-immonotherapy such as FCR or Bendamustine -Rituximab or BR) is shrinking. Who benefits is a shrinking pool of CLL patients with very specific demographics and FISH findings and the good news that they are mutated. This argues strongly that we should never consider FCR without first knowing our mutation status and our FISH results.

The debate is whether there is any role at all for CIT even in that select population.

The question how intense the CIT protocol should be or what is best approach may soon be moot with all the new kinase inhibitors changing everything, but at ASH 2013 a few months later we did learn that FCR has deeper longer remissions than BR but at the price of more toxicities, so the answer is as always in CLL: It depends on the patient. More on this ASH abstract later

Listen to Professor Hallek discuss who should consider CIT and who should not.

iwCLL 2013: Dr. Michael Hallek Discusses Clinical Trials in Germany versus the USA and BR versus FCR

Happy New Year.

I am in Alameda, enjoying babysitting my 7 month old and 2 1/2 year old granddaughters. Needless to say, finding a second to get any work done is tough, but the joy of being with them makes my inefficiency a small price to pay.

Today, I am returning to share additional relevant interviews from iwCLL a few months ago.

In the first part of my interview on September 11, the last day of iwCLL 2013, Professor Hallek first discusses some of the differences in clinical trials on either side of the pond.

One subject Prof. Hallek does not mention is the greater willingness of European patients to be randomized in a trial. Canadians and Americans prefer more control in deciding their therapy, and that helps explain the generally lower accrual in North American studies that have two or more randomized arms. I admit that one reason I was drawn to my trial, the official title being,  An Open-label, Phase 1b/2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, and Ofatumumab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Prolymphocytic Leukemia, was that I was assured that I would be getting PCI-32765, AKA, ibrutinib, AKA, Imbruvica. Phase 3 trials rarely offer that certainty, unless there is a cross-over and that is a big ongoing issue.

Keep in mind that the  calculus of accrual is entirely different when we are looking at the new non-chemo agents, where trials offering some of the exciting new drugs have filled at record rates.

Also don't miss the professor's definition of young.

I like it.

Next, Prof. Hallek, presages with great accuracy what was going to be announced a few months later  in at an abstract presented in New Orleans at ASH 2013, namely that BR is gentler on the marrow, but less effective than FCR. His take on what to do with that data is the real gem in our conversation. Listen to how he describes tailoring of the therapy to the individual patient.

Dr. Jeff Sharman whose interviews have and will continue to pop up here, has a nice review of the ASH data on his excellent blog.

Here is Professor Hallek, who was very busy chairing iwCLL, so I very much appreciate his time.  Sadly when my flight to New Orleans was canceled, I had to also cancel my follow-up interview at ASH, but we get the full story here and from the abstract.

Many, myself included, wonder if the whole question of BR versus FCR is moot as the era of chemo-immunotherapy may be ending in CLL. We have spent many blog posts discussing this issue, and we aren't finished yet.

Here is Professor Hallek:



More soon.

iwCLL 2013: Dr. John Byrd Discusses the Role of Novel Therapies versus Standard Chemo-Immunotherapy

In the first part of my interview from iwCLL 2013 in Cologne, Germany, my doctor for my ibrutinib trial out of Ohio State (OSU) gives us his take on two of the pressing questions facing us patients.

First, what is the going forward role of chemo-immunotherapy?

Remember that FRC offers those with specific favorable markers a 60% chance of a greater than a nine years MRD negative survival. That is beginning to smell like a cure, but at what price?

Based on his experience with over 400 ibruitinb patients, listen to Dr. Byrd's take. He calls upon the experience with imatinib (Gleevec) in CML to illustrate his point. Not every agrees with Dr. Byrd, but I do.

Next I ask about the vexing issue of residual disease with these new agents. Dr. Byrd is not worried. Hear his reasoning.



On a personal note, I am off to a very frantic ASH meeting tomorrow. Expect on the fly updates.

Still sick and miserable, but I am not I will recover.  Coughing less with a normal chest and sinus x-rays More of a head cold now. I also have been hampered by a cracked computer screen and broken eyeglasses, but the show must go on.

iwCLL 2013: Live from Cologne: The Opening Ceremony and Reception

Let me just say that this is going to an amazing conference. An Cologne is old worldly and charming, though vegan food will be a challenge. I am hoping I can find some time to wander the cobblestone streets and visit the Gothic cathedral. It was the tallest building in the word until the Eiffel tower was erected. And it took over 600 years to complete, started in the 1200s.

This is going to be a small but very concentrated conference on one subject only: CLL.

How concentrated?

In one row, attending the opening ceremony was Peter Hillmen, Kanti Rai, Carlos Croce, and Tom Kipps.

Talk about the who's who.

I heard about when to stop FCR (maybe sooner than 6 courses in MRD negative), epigenetics and some surprising and competing theories on clonal evolution, immune therapies, patient friendly clinical trial and this was all at the reception and opening ceremonies, which is not the scientific part of the meeting.

I got to get some sleep for a big day tomorrow.

 Michael Hallek Welcoming US to iwCLL 2013

 Professor Hallek and me

The reception (no vegan snacks, but I did enjoy a taste of the local beer, made only in Cologne)

Waiting for perfect knowledge?

It is always easy to tell when it is too late or too early to start therapy.

It is always easy (at least for me) to second guess any disease management decision.

It is never possible to get it all right and have all the facts.

So what to do?

For me, the answer has always been to get the best information and the best advice from the best people, and then act and stay mindful.

Some choices, such as a transplant, mean that you can't always be aware or mindful. You are just going to be too tired or too sick some of the time. That is where you need a well meshed team of loved ones to be your ombudsmen and of experts to execute the plan. These two groups will keep their eyes on different pieces of the puzzle, but they must communicate. This combo will give you the best chance to handle most of the inevitable bumps on the road so that you can keep moving forward.

Which brings me to another topic.

And another golden nugget:

If you don't know where you are going, you will never get there.

Assuming my chosen path of rituximab and cyclosporin continues to work its biological magic, and my nodes melt away not just where I and Dr. Kipps can palpate, but deep in the darkness of my mesentery, do I pull the trigger on a second transplant, a second shot at a cure and not just a remission?

That would mean a preliminary course of higher octane chemotherapy such as FCR or bendamustine with R or O to further reduce the disease burden and weaken my T cells so that I won't reject the graft as I did last time.

Or do I play out the string a little further in a different direction? Avoid tried and true chemotherapy and engage a newer sexier tango partner, such as one of the tyrosine kinase inhibitor in clinical trial now that doesn't promise a cure, but just a longer and gentler dance.

The risky cure or the unproven promise of a long deep remission?

There is a yet another saying in medicine. This one speaks to the appeal of a new medication.

Better use a new drug soon while it still works.

Is this too cynical an approach? Weren't all medications newborns at some time?

Some "new" drugs (triptans) have grown to be old and trusted friends and other (DES) have been run off leaving behind a trail of shame and tragedy. Some (Penicillin G) have been mostly pushed aside by the newer models, and others (thalidomide) have risen from the dead to find new life in novel therapeutic fields.

So what do I chose?

The devil I know or the devil I don't know?

The honest answer is that I never really know anything fully.

Like the gift of any photograph, I get the truth, but it is always incomplete and always has a built in point of view.

The best I can do is to calmly contemplated the options, purposefully act, and stay aware.

And have my trusty team in place for when I can't.

CLL Diary: If pigs could fly, we'd all choose the perfect treatment

For those with CLL, you might benefit from a review of David's very thoughtful take on the recent German study showing that FCR is a game changer offering proof for the 1st time of a therapy that actually prolongs survival.

CLL Diary: If pigs could fly, we'd all choose the perfect treatment

His blog is full of good advice on CLL.