ASH 2013: Dr. Byrd on the New Data on Ibrutinib and Obinutuzumab in CLL (chronic lymphocytic leukemia)

In my final post from the last days of ASH 2013 (lots more to come from ASCO 2014), my doctor, Dr. John Byrd out of Ohio State (OSU) in the third part of our interview discusses the durability of the positive results with ibrutinib and the latest results with obinutuzumab. Here is the referenced ibrutinib trial. For the first part of my interview with Dr. Byrd, click here and for part two here. They are worth reviewing as we covered many of the novel up and coming therapies beyond the usual headline grabbers of ibrutinib and obinutuzumab that are the focus of this last segment of the interview.

Dr. Byrd reminds us that it is the usual suspects are the few unlucky ones who do relapse on ibrutinib, mostly those of us who have been heavily pretreated and/or are 17p deleted.

What is the happy surprise is that the side effects seem to get less common the longer we take Imbruvica and there is a hint (see this NIH research by Dr. Farooqui whom I subsequently interviewed at ASCO 2014), that our immunity improves. Certainly the number of infections diminishes over time.

Dr. Byrd also answers my questions on the exciting monoclonal antibody obinutuzumab (Gazyva) and the new study results presented at ASH.

There are many reasons to be excited about this antibody. Despite the fact that the trial was rigged by choosing the wimpy chlorambucil as its sparing partner, Gazyva is the first therapy when used with chlorambucil to show a survival advantage in the difficult to treat mostly elderly patents who have other medical problems (co-morbidities) such as kidney disease that may take many therapies off the table. This trial  is offering hope where there is a pressing need.

We get into some of the details of how the drug is different from other antibodies. Dr. Byrd discusses how its engineering was specifically directed to make it different and probably better than rituximab. We also discuss its potentially nasty and quick infusion reaction and why that may not be such a bad thing.

Enjoy Dr. Byrd.

ASH 2013: Dr. Byrd Discusses Dinaciclib and the Need for More New Drugs to Treat CLL (chronic lymphocytic leukemia)

ASCO 2014 in Chicago was whirlwind with important updates to all of us with CLL.

Since returning a week ago, it has been an even crazier pace, but over the next few weeks, I will be sharing what I learned and what we CLL patients need to know.

While waiting for the processing of the audio and video material from ASCO 2014, I am finishing up by posting the relevant ASH 2013 interviews.

In the first on a three part interview with Dr. John Byrd, my personal trial physician out of Ohio State, we look at the drug, dinaciclib, a cyclin-dependent kinase (CKD) inhibitor, similar to flavoperidol, that arrests tumor proliferation.

Flavoperidol is a potent but difficult drug to administer with a very nasty attitude. For many with 17p deletion, it was their only chance at a remission.

Dinaciclib is a kinder gentler drug, with a better safety margin or "therapeutic index".

Dinaciclib also works independent of the 17p pathway and so has potent activity in that most difficult to treat population.

The ASH 2013 abstract is available here.  I attended the oral presentation on the last day of ASH 2013 in New Orleans. Dr. Joe Flynn, also out of OSU, was the principal investigator and just one of the nicest guy ever. Another great CLL doctor we patients are blessed to have.

So what did the phase 1 trial data on these 52 most difficult to salvage patients show us with this IV drug.

Its impressive efficacy of 58% is essentially the same (57%) in the 17p and 11q group. Responses were also very durable. Tumor lysis was a small but real risk and there was one case of sepsis. The most common side effects were low blood counts (leucopenia, anemia, and thrombocytopenia). That fits with  how it works as a CKD inhibitor.

Sounds pretty good, but I bet you have never heard of it. And it will probably never become commercially available, even though it helped nearly 6 out of every 10 of the worst relapsed/refractory patients with 17p deletion who until very recently had very few real options.

It likely won't be marketed in part because it's given IV, but more importantly, because the new oral agents such as ibrutinib and idelalisib and ABT-199 and others have similar or better efficacy with fewer risks.

The bar has been set very high.

It's a business decision. Merck who owns the patent on the drug must compare the outrageously high cost to get to this new molecule to market with the shrunken market share when and if does gets there. Makes perfect sense to stop the drug development from a corporate perspective.

While I understand that every company must make decisions that are sensitive to their long term success and viability, these decision are sometimes (such as in this case) not a good thing for us patients.

As we get near the end of this segment of the interview, Dr. Byrd discusses the early research on the causes of resistance in the few patients, especially the 17p patients, that do relapse on ibrutinb. (I will have more on resistance from ASCO 2014)

We patients needs as many options as possible to help us in those desperate circumstances. Dinaciclib could have been a potent option.

I am glad that ibrutinib and ofatumumab are approved and that idelalisib is getting very close.

But we mustn't stop there. The CLL battle is going well, but it is hardly won. This is no time to let up on the research and equally important, the commercial development of these novel molecules.

Don't leave us patients stranded on third base.

Listen to our conversation from Dec 2013 on this and other topics:



There are two more informative interview segments with Dr. Byrd from the last day of ASH 2013 that I will be posting soon.

I was going to write the CLL story is in evolution, but in truth it is in revolution.

It helps me to understand these rapid changes by reviewing all the research steps that lead to progress or to blind alleys .

Due to my lack of funding, technical problems and mostly the antiquated and wrong headed ASCO policy of denying bloggers such as me access to their extensive press resources, much of my material from ASCO 2014 may be audio only recorded off site as required or the video shared through joint efforts with my friend and fellow patient advocate, Andrew Schorr and his team at Patient Power.

Despite these challenges, I am excited to be sharing the developing news from Chicago earlier this month.

ASH 2013: Dr. John Pagel Discusses the Risks and Benefits of ABT-199 and TRU-016 or otlertuzumab in CLL (chronic lymphocytic leukemia)

In the final segment of my interview with Dr. Pagel from ASH 2013, he discusses ABT-199 and TRU-016 or otlertuzumab (yet another mouthful for us to poor patients to learn and pronounce).

We have heard much already about ABT-199. Here is a link to a trial reported at last year's ASCO meeting and I have an interview pending from ASH 2013 with Dr. Seymour from Australia. At ASCO later this week, there will more news on ABT-199 with a new dosing schedule to reduce the risks of tumor lysis syndrome (TLS).

TRU-016 is another under reported therapy, a potent monoclonal antibody (MAb), much like rituximab, that is as of now only available in clinical trials. In my opinion it has not received the attention it deserves. Unlike rituximab or ofatumumab or even obinutuzumab that all target CD20, TRU-016 targets CD37. But like CD20, CD37 is also found on most mature B cells, both cancerous and benign and much less so on T cells making it is a good choice for fighting CLL. That's an important difference from Campath that binds to CD52 and destroys both B and T cells. With no T  or B cells to fight infection coupled with our already wimpy immunity, we are high risk for life threatening infections. TRU-016 did not increase infection risk in this small trial.

Here is the ASCO abstract that compares bendamustine with or without TRU-016. The number were very small, but for those who received TRU-016 there was responses in the two patients with 17p mutations but not in the two with 17p deletions. As expected, there were no responses to single agent bendamustine.

And here is Dr. Pagel:



I am hoping to sneak one or two more post before I take off for ASCO 2014 later this week.

ASH 2013: Dr. John Pagel Speculates on the Future of CLL (chronic lymphocytic leukemia) Therapies including the late breaking data on Idelalisib

In the second part of our interview at ASH 2013 we shift from discussing radio-immune therapy and listen as Dr. John Pagel starts by agreeing with many of us patients that our future could and should see less and less chemotherapy and more and more combinations of targeted therapies.

He then gives his perspective on the late breaking abstract at ASH on idelalisib (AKA CAL 101 AKA GS-1101) plus rituximab versus placebo plus rituximab that Dr. Furman and I also discussed in this prior post that also contains a link to the ASH abstract and the NEJM where it indeed did get published. This trial has been well reviewed in the past, but it was nice to note the agreement among the researchers involved in this large trial.

Here's part two of the three part interview.



More to come soon with the last section of Dr. Pagel's interview and a long three part interview with Dr. Byrd from the same ASH annual conference.

Then all the attention turns to ASCO 2014. ASCO covers all cancers, so CLL is a minor player compared to the big four of breast, colon, lung, and prostate, but there will be important new data on ibrutinib, idelalisib, ABT-199, ONO-4059, a new SYK inhibitor from Gilead and others.

I have several exciting interviews scheduled both in video and simple audio format that I will be posting and sharing with my friend Andrew Schorr on his patient friendly cancer website Patient Power as Andrew made the sensible decision not to fly from Barcelona to Chicago. Andrew's team will also be posting the latest news on several other types of cancer, some of which may have directly relevance to those of us with CLL.

ASH 2013: Dr. John Pagel Discusses Radio-Immune Therapy (RIT) in Chronic Lymphocytic Leukemia (CLL)

The big buzz at the ASH annual meetings for the last few years has rightly been targeted oral therapies such as ibrutinib and idelasib and other, but one therapy that in my opinion that has received short shrift is radio-immunotherapy or RIT.

In fact, it is so rarely used that since this video was recorded in December, 2013, Bexxar (Tositumomab) was pulled from the market in February, 2014 as it was prescribed fewer than 75 times in 2012.

Zevalin (Ibritumomab Tiuxetan) is still available.

At ASH 2013, I interviewed Dr. John Pagel out of the Seattle Cancer Care Alliance (the union of the Fred Hutchinson Cancer Research Center (the Hutch), UW Medicine, and Seattle Children's) who has a very patient friendly way of explaining how these drugs work and what their role might be. Dr. Pagel is also a kind and wise transplanter and as such has extensive experience with conditioning therapies that often include different forms and dosing of radiation to prepare for the transplant and that is another reason why I wanted to hear about his updated research on this important and neglected corner of CLL research. To understand how much or little we have moved forward in the last year, please check out my interview with Dr. Pagel done a year earlier at ASH 2012. As you can read, we are still dealing with the  some of the same old issues that are slowing our progress.

RIT makes most sense to me as a mop up  or "consolidation" therapy and as I have posted before, we desperately need that. I believe RIT should be explored as a final knockout punch to our CLL when it has been decimated and only a few active cells are hiding out in our marrow and our nodes.

I suspect that this research idea won't get much traction.

Dr. Pagel is too kind when he describes why these antibodies with their toxic payload are underutilized.

True they are expensive and tricky to administer, but they are usually a one or two time treatment. 

Sounds good to me. 

The real reason they are not used as much as they could be is that oncologists can not prescribe them. You need to consult a radiation oncologist and even then, the radiation oncologist you see may not offer that option or have much experience with RIT. It requires specialized set up for its administration and management. 

So basically it is a turf issue. 

Here is a link to the abstract that Dr. Pagel presented at ASH 2013.

And here is the interview. As I said as we talked, I love his analogies.

ASH 2013: Dr. Neil Kay on Why We Need a CLL (chronic lymphocytic leukemic) Expert and on Clonal Evolution

Dr. Neil Kay is Professor of Medicine at Mayo Clinic and also is fellow Canadian who had dedicated his career to helping those of us with CLL through research and direct patient care.

I interviewed him in New Orleans at ASH 2013.

His research has been wide and varied including the studies on EGCG (the active ingredient in green tea) that was sponsored by CLL Topics and Chaya Venkat that looked to see if there might be role for this specific extract from green tea as a gentler and more natural way to control our disease. Turns out it did have some significant efficacy, though its effect were not too powerful.

I miss what Chaya and what CLL Topics did for our community. Much of my work is an effort to pick up where she left off, but those are big shoes to fill.

In our interview form December 2013, Dr. Kay hits us with the cold facts that support my long time mantra of getting a CLL expert to head up your team. His published study has proven that we have better outcomes if we have a CLL expert on our team.

He and I discuss our shared vision of the perfect treatment team.

I can not overstate how important this is to our success in our long duet with our CLL, our nasty dancing bear of a partner. It can determine who will leads and who will follow, and how often we will get our toes stomped or worse, how often we will be forced to endure unwelcome advances by our disease.

The second topic we grappled with is more complex but worth the effort. It has to do with CLL clonal evolution.

Turns out p53 (often but not always related to a 17p deletion) is only half the story.

Turns out CLL is not a genetically stable disease. No surprise there. Especially true if you are unmutated or missing 17p.

Turns out the problem may be baked into the cancer from the start, to quote Dr. Kay it may be a "resident property of a patient who presents with CLL" and that treatment does not induce the new clones but allows what were once minor subclones to grow and become dominant. And that can spell problems for us as those clones are nearly always more aggressive and resistant to treatment.

The lessons from this research help inform us about the biology of how our cancer relapses and more importantly, about how it becomes refractory (resistant to therapy).

Dr. Kay admits that this research predates the new signal inhibitors such as ibrutinib and idelalisib and ABT-199 and more. How their use will impact the evolution of the CLL clones and subclones is a story that is not yet understood, but we can learn from this important research.

His explanation is crisp and clear. Understanding what his collaborative research has uncovered by looking at genetic evolution of CLL should help inform our decisions about when and how to treat our leukemia.

The second part of the interview will follow soon.

ASH 2013: Dr. Furman: Idelalisib in Fragile CLL (Chronic LymphocyticLeukemia) Patients

I am going to be busy posting several videos from ASH 2013 because some of the new data that I will be discussing from ASCO 2014, May 30-June 3 in Chicago will be the longer term follow-up data from the same studies.

Today is a short interview with Dr. Furman on his late breaking abstract presented at ASH 2013.

Dr. Furman was the lead investigator and author in this important NEJM article, arguably the world's  most prestigious medical journal. Dr. Furman, out of Cornell Weil, was deeply involved in the first in human trials of both ibrutinib and idelalisib. This important post from only one year earlier at ASH 2012 seems like ancient history as we have learned so much more about these game changing treatments. Worth reviewing to see just how far we have come in such a short time.

The study that we are discussing in the video (click here for the abstract) is pretty interesting for many reasons.

The first is the the particular population that was targeted.

I have blogged in the past about how we determine whom is fragile and whom is elderly. The CIRS score is one way to quantitate how sick we are besides having the obvious problem of CLL that needs treatment.

The group that was studied here was those of us who were likely not be able to tolerate a full course of chemo-immunotherapy due to our co-mordid conditions.

Turns out this group was also a tough group to treat too. 80% were unmutated and 45% had the dreaded deletion at 17p.  

This combo of fragile and tough to treat patients is a group that until very recently had few options and so I commend the researchers for looking to these neglected group.

The next interesting aspect of this trial was that it was placebo controlled. One arm was just single agent rituximab and isn't rituximab alone a pretty wimpy comparator? Dr. Sharman and I discussed this in some depth in a prior post. I recommend you review it. That way you will have the opportunity to hear from an important CLL researcher and also from the lead investigator about this same study.

And it did build in from the get-go a cross-over for those who progressed which for me mitigates much of the ethical problems with the trial design issue.

The adverse event profile is encouraging. One case of Richter's. As CLL is being better controlled, Richter's is becoming too often the cancer's escape route

Next, take a look at the data itself. It was very very impressive.

Finally, Dr. Furman gives his perspective on how this study and the other news out of ASH 2013 is influencing therapy choices for not just the fragile CLL patient, but for all of us.

Dr. Furman has been a pioneer and visionary in moving away from chemo based therapies of CLL. I am grateful for what he has done and even more so for the brave patients that have entered his and  others' clinical trials, especially the more risky early phase 1 trials. Without their courage, there would be no progress.



Much more to come soon.

I just learned that I will be lecturing on CLL to primary care providers at the Baltimore Convention Center on June 28. This is an introductory lecture with videos from interviews with Drs. Kipps and Wiestner and others. I'll be there June 26-29 and leave from there for Columbus, OH for every 84 day visit to Dr. Byrd in my CLL trial at OSU. Talk about having skin in the game. Please come, hear the lecture and visit. The day before I will be also speaking on gout and CAM. See this link below for my US lecture "tour"  schedule. This will be for CME, continuing medical education, that is intended mostly family doctors but many sophisticated patients find the presentations very helpful. And it's free. I would love if you could drop by and say hello.

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.

ASH 2013: Dr Jeff Sharman Discusses the Ideal Design of Phase 3 Trials with Novel Agent versus the Reality in the Community

As a patient, it is easy to be critical of study design.

Case in point: The phase 3 trial of rituximab (R) plus idelalisib (I) versus rituximab plus placebo presented at ASH 2013 in New Orleans.

Wait a minute, we patients scream. One arm of this trial is offering us a monotherapy option that is not recommended by most CLL experts because it produces a lousy response rate in the middle single digits. In the trial, lymph node response rate was a meager 4% for the R+ placebo versus 93% for the arm with the two active agents. And the duration of the response for the R alone is less that six months.

In comparison, in the R+I arm, median progression free survival has not been reached, and remarkably, even overall survival was improved, something unheard of in CLL just a few years ago when FCR was shown to be the first drug combination to add years to our lives.

All the data from the late breaking abstract can be accessed here. It is powerful, but one must ask, does idelalisib look so good because it was being compared to a straw man?

Is this an ethical way to conduct a trial?

Dr. Jeff Sharman, a regular on this web site, is both a community based oncologist and the medical director of hematology research for The US Oncology Network.

He points the pros and cons of the controversial trial design.

Watch the video and form your own opinion before I give you my bottom line.

First Dr. Sharman does a good job reminding us the difference between a phase 1, 2 and 3 trial.



So what do you think?

At first,  I was dismayed by the trial, from a patient's perspective, but when we have a trial design where we are pretty much guaranteed that we will get idelalisib if we need it, and in either arm we  can avoid chemotherapy, on further reflection I am more sanguine about this kind of trial.

The science bothers me more than the ethics. In the study, the results with idelalisib are very impressive and would likely have stood up to a much more active comparator arm, but in this case it was a massive mismatch as evidenced by the unheard of gargantuan P number (p = 1.3 x 10^-30 ). In other words, the odds of getting this result by chance alone was not one in a million or one in a billion or one in a trillion, but about one in 10 followed by 30 zeros.

So what is my take away message?

First, I am OK with most trials that have a cross-over built in from the get-go, and especially fond of those that offer us a chance to avoid chemotherapy.

Second, idelalisib is clearly going to be a powerful addition to our armamentarium for treating CLL. 
In this study it took on a tough bunch of patients.The median number of prior therapies was three. The test subjects were all considered too unhealthy to get traditional chemotherapy. Nearly half were 17p deleted and 17 out of 20 were unmutated. We are told that all the risk groups responded better to the idelalisib arm, but the abstracts doesn't give us much detail.

So, bottom line, unless my need to get my disease under control was so acute that I could not risk the delay in getting a response if I was randomized to the R+ placebo arm, I wouldn't hesitate to enroll in a similar trial if I needed therapy.

Based on this and other positive studies, I hope and suspect idelalisib will be approved for CLL in the USA before the end of the year. And that will be a good thing for the CLL community.

ASH 2013: Jan Geissler & Giora Sharf Part 2 on Adherence, the High Cost of Cancer Medications, and the Importance of Clear Communication

In the second part of my interviews from ASH 2013 with two smart patient advocates in the CML world, Jan Geissler and Giora Sharf reveal the results of their important study done in conjunction with their non-profit umbrella organization, The CML Advocates Network.

Before I get too far into my analysis of the results, let me first applaud Giora and Jan for doing all the hard work in making this possible.

Not only did they recognize an unmet need, they realized that their opinions would only be respected with valid research backing them up.

Then they had to not only design, develop, and ultimately score, review, interpret, write-up and present the data, they first had to procure the funding, find the doctors willing to help, and have developed over years a strong participating network of patients ready to jump in and help.

As someone in the throes of establishing a new CLL-focused non-profit organization, let me assure you, none of this comes easily. It was earned with hard work and trust.

More news soon on how this nascent disease specific non-profit will benefit anyone touched by CLL in very focused, local, unique and practical ways while not recapitulating what is already being done so well by the LLS and LRF, two great organizations that supply excellent background disease information and much more and also provide high quality large group meetings with top flight reviews of the basics in CLL in their breakout sessions. Here is my report from the last LRF meeting. I was also privileged to be asked to volunteer to speak on self advocacy this past weekend at the LLS Blood Cancer Conference in Los Angeles. I plan to share those slides I developed here and on the LLS web site soon.

Our new non-profit will be working with smaller interactive groups and be strongly focused on the cutting edge of research. More to come. I am so excited. This will make a high difference.

But I digress.

If you haven't seen the first part of the interview or you just want to revisit it, please click here.

If you want to read their fine paper, please click here.

The first few minutes of this section of the ASH 2013 interview identifies some of the high risk markers for skipping our medications.

Later we discuss the issue of the high cost of the medication. Not surprising this is a well recognized risk. Should I eat or take my pills?  For more on this important issue, browse through my blog and take a look at this paper on cost of oral medications and adherence in CML.

Many pharmaceutical companies (see the You & I Access program as an example for ibrutinib) have generous program to help defer the cost. The LLS can be a big help, but properly constructed, well conceived, and revenue neutral oral parity laws (where the percentage of the cost borne by the patient for oral drugs and IV drugs is similar) are not only possible but are desperately needed to avoid all these welcomed but ultimately stopgap measures.

Finally, as Jan says: "Adherence is partnership." The patients, the doctors, and the patient groups getting the word out about the importance of clear communication and understandings.

Ultimately good communication is the most critical and fortunately the most malleable piece of the puzzle.

Here is the video:

Please pardon the abrupt finish. You didn't miss anything but a technical glitch.

More soon from ASH, more on adherence, and more about the new non-profit to help those of us with CLL with better support and communication.

ASH 2013: Giora Sharf and Jan Geissler Discuss Mediation Adherence or “Drugs don’t work in patients who don’t take them.” – C. Everett Koop

I am introducing a new subject, namely the importance of taking our medications as prescribed.

What we call this simple behavior has been undergoing some changes as we have shifted from the more paternal old school term of "compliance" to the newer shared decision making model inherent in the recently most popular term "adherence". 

I  wrote an entire article on this important semantic issue a few years ago and will be updating it here as there has been further evolution in this topic of what these world imply about our world view.

I plan to spend some time on this subject over the next few months because it becoming increasingly important to all of us with CLL, in fact to any of us with any chronic disease.

This is especially true in the cancer world and there is much we can learn from the poster child of game changing targeted therapy where you simply swallow with a glass of water, imatinib or Gleevec, and poof….your cancer is no longer an issue.

It is hard to exaggerate the importance of the development of imatinib. For CML (chronic myelogenous leukemia) patients it changed a former life ending cancer (unless you had a successful but very risky bone marrow transplant) to a chronic disease controlled with taking a pill. The development strategy involved also fundamentally changed forever how all cancer could ideally be controlled.

Ibrutinib and idelalisib and all the new oral meds or TKIs are products of the process that was first so successfully deployed with Gleevec. First understand the biology of the cancer, figure out what is uniquely driving the malignant cells and then block it and try to block little or nothing else.

Targeted therapy.

The Pulitzer Prize winning book, The Emperor of All Maladies by Siddhartha Mukherjee is must reading for anyone dealing with cancer, and much of it is about the history of imatinib.

But even a wonder drug doesn't work if we don't take it. 

30% of CML patients are not taking their life saving medications, and that is the leading cause of developing resistance to therapy.

So please listen to what my friends from the CML world have to say about adherence from ASH 2013.

Giora Sharf and Jan Geissler are not physicians but CML patients turned advocates and researchers  who presented important research at ASH about why people don't take the pills that are saving their lives.

Here is part 1.

More on this and other news from ASH soon.

ASH 2013: Dr. Jennifer Brown Discusses the New Data on Obinutuzumab (GA-101 or Gazyva)

At ASH 2013, there was much to celebrate for those us with CLL.

This interview was recorded immediately after Dr. Jennifer Brown of Dana Farber had moderated an exciting CLL press conference in that same noisy press room.

While the small molecules that can be taken orally such as ibrutininb, idelalisib, ABT-199 and even the newer IPI-145 and ONO 4059 may have hogged much of the headlines over the last few year in the CLL world, there was important news about a new and better monoclonal antibody or mAb, namely obinutuzumab.

This one, like rituximab and ofatumumab, is directed against CD20, a surface protein found on all B cells, good and bad.

So like its fellow anti-CD20 mAbs, obinutuzumab knocks out all our B cells, leaving us at an increased risk for new infections and reactivation of old ones such as hepatitis B.

A bit of a background on another mAB first.

I have to say after all the excitement following the the approval of the second generation fully humanized CD20 antibody, ofatumumab, I have been disappointed in the results. Its main advantage seems to be for anyone allergic to rituximab, lovingly called "mouse juice" by the thousands of us who have had it dripped into our arms at infusion centers across the world because of its unholy but magic mix of mouse and human proteins (especially strange to think about if you are vegan like me). Despite high doses of pre-medications with steroids and antihistamines, some of us patients just can't get our bodies to stay calm in the presence of the mouse antigen and let the antibody do its important work. That is where ofatumumab has shined. No mouse proteins, so those who could not tolerate "Vitamin R" had an option. But the impressive improvement in efficacy over rituximab that I and many others were hoping for has not really materialized.

Obinutuzumab tells a different story. People are living longer significantly longer as Dr. Brown will detail on camera. The results are clearly better. The bar with rituximab was already set pretty high. Rituximab might be a lousy CLL drug on its own, but as a dancing partner it makes everyone look like a Fred Astaire (or Ginger Rogers). Its addition to FC forming the "gold standard" of FCR was the first time that any therapy was shown to prolong survival in CLL.

Dr. Brown of Harvard now gives us even better news on obinutuzumab.

But first we review how it was engineered to get these strong results and explains why being the first type 2 anti-CD20 antibody is so important to its efficacy.

And she discusses the management of the higher risk of infusion reactions. Please remember that although these new antibodies have no murine proteins, they can still cause rather severe infusion reactions, precisely because the bind so strongly to our B cells and are such potent killers.

Here is Dr. Jennifer Brown:



Remember too that this drug is already approved for CLL. From the package insert: in combination with chlorambucil, is indicated for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL).

As I have reviewed in a prior post, this is a very limited indication, and much of its benefit would be expected to come in its use with other more potent combinations than with chlorambucil and for patients who have relapsed or who are refractory to other therapies including other mAbs. I would hope that it appropriate use off label is not rebuffed by the payers.

I expect soon to see a growing number of trials mixing and matching the new TKIs with obinutuzumab to get us that elusive CR. We need more trials. To get to our ultimate goal, a cure, we must first get to and pass CR, and most of the TKIs are leaving stalled on 3rd base with some persistent measurable disease. These new oral wonder drugs still need a teammate to get us home to a cure, and obinutuzumab is a very strong candidate to play that role.

That is the future I want. Rational non-chemo combinations edging us closer to a cure. It can't come soon enough. But we need more creative trials and more brave risk takers to make them happen.

ASH 2013: Dr. Adrian Wiestner Discusses Prognostic and Predictive Factors, the Nuances of 17p deletion and Residual Disease

Merry Christmas.

In the second part of the interview from ASH 2013 in New Orleans, Dr. Adrian Wiestner from the NIH gives us some very carefully considered reflections on the news from the cutting edge changes in our understanding of CLL.

I first asked him to revisit the important issue of predictive versus prognostic factors that I first discussed at iwCLL with Dr. Sharman.

His review of 17p deletion, particularly for those lucky few who are mutated with 17p is very hopeful and nuanced. Listen carefully.

Dr. Wiestner suggested a cut off of 25% to define high risk 17p deletion. The reality is that it depends. While Dr. Tam's research in Blood on de novo 17p del (from the time of diagnosis and not first appearing after treatment) find prognostic significance only when more than 25% of the nuclei are missing the small arm of one of the 17 chromosome, others suggests a lower cut of 20%, some 10%, and some as low as 5% in looking at all cases, de novo and acquired, of 17p deletion. Like many subjects in CLL, consensus is lacking.

My simple take is the less 17p, the better. None is the best.

And we all know that the less disease, the better. Dr. Wiestner points out the obvious but we we need to hear it: You have to get to MRD (minimal residual disease) negativity to get to cure. What does this mean for the new drugs that rarely seem to get to CR, let alone MRD negative? Dr. Wiestner shares some thoughts.

Keep in mind also that 17p is a bad player in that not only does it not allow apoptosis (cell suicide) in response to most chemotherapy and thus rendering common CLL drugs such as fludarabine and cytoxan most ineffective, it also allows the cancer cells to mutate (genomic instability) with no controls on a clone gone bad. Add this clonal devolution to a significant population of residual cancer cells and we begin to understand why initial responses to the new agents such as ibrutinib and idelalsib are excellent, but sadly late relapses are more likely in those of us with a deleted 17p.

This seems to me to be a strong call for dual therapy for the 17p population, but whether that is the answer will only be answered with clinical trials.

Let's listen to Dr Wiestner.



We are so lucky to have a team of doctors working to solve our issues.

More interviews soon.

ASH 2013: Dr. Wiestner Discusses Why Therapy in CLL Needs to be Individualized

In the first of my video interviews from ASH 2013, Dr. Wiestner of the NIH outlines in some detail just how heterogeneous a disease CLL is now understood to be.

Dr. Wiestner points out that the groundbreaking work of the late Dr. Hamblin on mutation status is now  much nuanced.

What this new understanding demands is a different approach for every patient based on their biology and their personal preferences.

This is a future that I can buy into.



I will be continuing to publish interviews from both iwCLL and ASH and share my take on some of the important ASH papers.

This short post is brought to your from the free internet offered at the Athens airport as I start my long trip home after meeting with some other blood cancers advocates in Athens, and having an amazing time enjoying new Greek friends and and ancient Greek sites.

More on both soon.

Life is good.

ASH 2013: A Quick Perspective

After five frantic days of attending very detailed and jargon filled lectures full of the latest CLL news, reading hundreds of complex poster abstracts and discussing them with their authors, interviewing many CLL experts from around the world balancing their crazy schedule with the limited availability of space for the interviews, meeting with leukemia and lymphoma advocates from everywhere and forging new alliances, brainstorming with CLL experts about research design, shared decision making, and the patients' perspective, and talking with members of the pharmaceutical industry about supporting what I would envisions as the unmet needs for the CLL community, I am heading home with much hope and much to share.

This was an amazing ASH conference for those of with CLL. Expect surprisingly candid videos and challenging discussions.

I don't just ask the the easy questions. I am looking for signals that might hint at trouble down the line. I am not there to make the doctors or the drugs look good, but to dig for the truth. I am not there to throw a hanging curve ball, but to scorch a fastball on target and see how well it is handled.

That said, it was handled very well, and the for the most part, the drugs and the doctors, do look very good and the news for us is very exciting and full of promise.

So many positives, and a few cautionary tales to come.

More soon.

I will be posting several remaining videos from iwCLL, but I will be mixing in some of the new ASH stuff too.

But first, I need some rest and relaxation.

My respiratory infection is mostly but not completely gone.

Tonight will be my first chance to walk around the Quarter a little and maybe catch some Zydeco music. I can't leave NOLA sans laissez le bon temps rouler on Bourbon Street for at least for a few minutes.

ASH 2013: The Joys of Travel

What else could go wrong? Horrible respiratory infection (getting better), cracked computer screen (replaced), broken eyeglasses with a missing lens (found and repaired with one of those cheap kits you buy at check-out), and now our flight is canceled to NOLA for ASH 2013. Painful to have to cancel all the interviews that I had worked so hard to arrange, especially the very much in demand Professor Hallek. The best I could do after hours on hold has us arriving tomorrow morning on a pricy flight from LAX to Baton Rouge on a different airline. Then a long and expensive shuttle ride.

But I am busy texting and emailing and trying to reschedule what I can. And hopefully I can sleep a bit on the plane and shuttle.

Thankfully, most of the interviews don't start until tomorrow afternoon, but the rearranging means I may need to miss some of the lectures that I wanted to catch.

I can't do everything. Can't be everywhere at once.

I still expect ASH 2013 to be a stellar meeting for those of us with blood cancers, and I expect to be back in my stride by tomorrow.

This is all fixable stuff. No big deal. Minor annoyances. As those of us with cancer know too well, that is not something that we can always say.

Expect a brief update tomorrow, late.