Sunday, November 30, 2014

ASCO 2014: Dr. Susan O'Brien Reviews the 3 years follow-up Data on Ibrutinib in CLL (chronic lymphocytic leukemia)

If you can handle more hisses and pops on an audio recording, you will get to hear some pretty exciting news from Dr. Susan O' Brien who incidentally is leaving MD Anderson after many years of important CLL related research and compassionate patient care to head up a cancer research team  and consult on CLL patients in my backyard at the University of California at Irvine (UCI) starting Jan. 1, 2015

During the interview, Dr. O'Brien shares the three year follow-up data on single agent ibrutinib in relapsed and refractory patients and in the elderly.

In her important ASCO 2014 abstract, published 6 months ago, the data is astonishingly good for those lucky enough to get ibrutinib frontline, the over 65 crowd, a strong argument in favor of moving it and other drugs such as idelalisib or ABT-199 upfront.  In this trial, in the treatment naive arm, there was one early progression with Richter's that was probably there before the trial even began, and the rest of the cohort remains in the happy land of PFS also known as progression free survival.

The data is still very good for the difficult to treat relapsed and refractory group, but the curve is not flat. Relapses happen. This is especial true for those of us like me with the dreaded 17p deletion, where half the patients have started to progress after a little more than two years. While this is clearly much better than anything else out there in this most challenging population, ibrutinib has not hit a home run for this group as it might have for the treatment naive patients.

Despite significant recent progress, effective long term therapies for relapsed 17p deletion still remains one of the more pressing unmet needs in the world of CLL.

Dr. O'Brien discusses what these relapses look like, and mentions a strategy that I would strongly consider, namely that even at the time of relapse, one stay on ibrutinib until a new therapy is begun, as the BTK inhibitor, even it is no longer irreversibly binding, it is still partially braking the disease progression.

Let's listen to Dr. O'Brien.

Again sorry for the audio noise. Once these final ASCO interviews are posted, I promise I will not only be notching up the quality of what you see and hear about CLL here and elsewhere, but with the help of many others, will be expanding into whole new realms of education and support to meet the unmet needs of our community. Stay tuned.

Labels: , , , , , , ,

Saturday, November 29, 2014

ASCO 2014: Dr. Sharman Reviews the Results and Implication of a Single Agent Obinituzumab Poster in CLL (chronic lymphocytic leukemia)

Another audio interview from ASCO 2014, this time with the ubiquitous Dr. Jeff Sharman, who with his work heading up a large national CLL/NHL research group, has brought us several important clinical results that has advanced our understanding of treatment options and provided directions for further research.

Here he is part of a group with Dr. Joe Flynn as the lead author, studying two different doses of the  fully humanized monoclonal type II antibody directed against CD20 (same target used by rituximab and oaftumumab) known as obinituzumab, also known as (AKA) GA101and AKA Gazyva used in this trial as single agent.

The abstract shows a strong trend to a better response with the higher dose, especially as regards complete responses. This is not surprising when we know from a dose escalation trial of rituximab published in 2001 from Dr. Susan O'Brien (mentioned in the interview by Dr. Sharman), that when it comes to antibodies, more is better.

Makes sense based on what we know about how these antibodies work. There are billions of B cells and only so much antibody. When they are all "bound up", there are none left.

There is also research now looking to see if there is similar dose response relation with CAR-T therapy: the more chimeric T-cells, the better, though the story here is much more complicated as it seems CAR-T cells are serial killers.

Dr. Kipps and I also discussed this same paper and the difference between Type 1 and Type 2 antibodies here. Dr. Jennifer Brown discusses earlier research on GA101 at ASH 2013 and the different types of antibodies here. And here are the details of its FDA approval and some of my comments only published only a little more than a year ago.

And if that's not enough background, here is an editorial from Blood 2012.

What a great year it has been for those of us touched by CLL! We are all on a fast moving train and while cure is still a distant light in the tunnel, long lasting low toxicity disease control for most of us may be a whistle stop that we blown past some time without even noticing some time last year.

Here's hoping.

Enjoy the audio interview with Dr. Sharman.

Thank you for putting up with all the pops and hisses again. I promise that they will be a thing of the past once I finish uploading the audio from ASCO 2014 and move forward to ASH 2014 and beyond.

Stay tuned as we have big plans that I will be announcing here soon that will improve our options for education and support for all of us with CLL and related B cell lymphomas in the near future.

Labels: , , , , , , , , , , , ,

Thursday, November 27, 2014

ASCO 2014: Dr. Byrd: Ibrutinib in the Real World of CLL (chronic lymphocytic leukemia)

In this short second half of my interview from the final minutes of ASCO 2014, Dr. Byrd, my clinical trial doctor at OSU, discusses some of the potential  pitfalls in receiving ibrutinib outside of a trial from a provider who perhaps has little or no experience with the drug.

That is one of the reasons I push so hard that we patients be well informed and engaged so we can be be sure we are getting the best possible care.

It is also a push to strongly consider a second opinion, especially when we are considering therapy  with a doctor where the bulk of the practice and research is devoted to the care of CLL patients.

Ibrutinib and some similar other targeted oral medications (kinase inhibitors) are quite safe and easy to use, but do have some unusual characteristic effects.  For example it is common to experience a rapid climb in the lymphocyte count at the start of therapy. You and your doctor need to appreciate that it is not dangerous or a sign of progression or even really an adverse event. It is just a redistribution of the lymphocytes from the nodes to the blood whether there are more vulnerable and more likely to die.

Again, please pardon the pops and hisses in my part of the audio during the interview.

I have several great videos on tap from Greece (ESH International Conference on New Concepts in B Cell Malignancies: From molecular pathogenesis to personalized treatment) but they are embargoed until after ASH.

And of course, I will be attending ASH 2014 next week with my one man video production team to bring the latest news, commentaries, and explanations.

I go as as doctor, a patient, a reporter and I hope as your advocate. It can get pretty crazy: a scheduling nightmare and long demanding days.

On a personal note, my labs remain stable even though I have been off cyclosporin for my auto-immune platelet issues (ITP) for almost two months. The one fly in the ointment is that my white count and absolute neutrophils are a bit high. That usually means an infections, but I feel well. Could be just stress and lack of sleep. It's happened before and returned to normal, never leaving a clues as to why it bumped it. With CLL, I have learned to accept that things just happen and I may never know why.

Here is Dr. Byrd.

Happy Thanksgiving.

Labels: , , , , , , , ,

Tuesday, November 11, 2014

ASCO 2014: Dr. Byrd: What we could only Learn from a CLL Phase 3 Trial about Ibrutinib and Ofatumumab in Relapsed CLL (chronic lymphocytic leukemia)

On the very last day of ASCO 2014 at the very last presentation, Dr. Byrd, my doctor out of Ohio State (OSU), shares with us what you could only find out from a Phase III trial.

But first I must apologize for all the popping from my holding the microphone too close to my loud mouth. Without any technical support for my audio recording, I did a lousy job on my own. But I have learned from my mistakes. Fortunately the important speaker in the interview, Dr. Byrd, is much more easily understood. Which is good because he has a lot of revealing thoughts and information to share. So despite the annoying pops, I decided to post this audio interview. There is a second section too on its way.

Dr. Byrd starts by explaining the important data that can only be discovered in a Phase III trial. Phase I is all about slow dose escalation and safety. While a Phase II trial is about watching for adverse events (AE) and sniffing around for efficacy, there is no comparator arm so anything bad that happens is automatically blamed on the trial drug to be extra cautious. But the bad happenstance may be just part of the background noise of the disease process, with or without the drug. There is no way to tell until we get to Phase III trials where we can see what happens and how often it happens to those on and off the novel therapy.

And we learned some surprises about AE with both drug with this trial. Here is a link to the abstract.

It also soon becomes abundantly clear to the trialists that ibrutinib was the far more potent drug for most patients. The difference in the responses with ibrutinib and with ofatumumab were so pronounced that all decent ethical standards forced a midstream redesign of the trial (and possibly all future trials) to allow a cross-over when there is such a wide gap between outcomes. Amazingly, even with the cross-over, ibrutinib still showed a significant survival advantage in the trial. That is good news for those of us on the outside looking in or those in the trial randomized to ibrutinib, but not for everyone: sadly it meant is that some patients on the ofatumumab arm had to die in order to prove the superiority of ibrutinib.

Dr. Byrd bravely and realistically takes on the issue of cross-over in trial design and getting drugs to market and those who need them.

He also discussed prognostic factors (the bad guys are the usual suspects: 17p deletion, complex karyotype, and perhaps three or more prior treatments). ASH 2014 will pick up this theme where it at least one abstract seems to say that complex karyotype is the ringleader of the bad players. I tend to agree. I have wondered aloud if 17p, the guardian of the genome, is just a surrogate marker for genes gone wild. This is personally annoying because I have a complex karyotype.

Later I think you can hear Dr. Byrd's pride in the new predictive tests that he and the team at OSU are developing to tell who is likely to progress on ibrutinib before they actually do.

Enough preamble. Let's listen to Dr. Byrd.

By the way, I wrote this entire blog post over the Atlantic Ocean on my way to Greece to lecture to hematologists on what patients want in their CLL treatment and also to attend and report from the ESH conference on B cell lymphomas.

Part two of my interview with Dr. Byrd to follow soon.

Labels: , , , , , , ,

Sunday, November 9, 2014

ASCO 2014: Dr. Farooqui on Trials at the NIH, ABT-199, and Issues of Long Term Oral Therapies in Chronic Lymphocytic Leukemia (CLL)

In my last video interview from ASCO 2014 (several audio only interviews to come), with help from my friends at Patient Power, I interviewed Dr. Mohammed Farooqui from the NIH on the research and trials ongoing at the NIH, his enthusiasm about ABT-199 and the questions he and others are researching on longterm use of the novel oral meds.

Do keep in mind that all trials at the NIH in Bethesda are all free, with or without insurance. They even help with your airfare and hotel, and they are open to any one in or out of the USA.

The natural history trial on CLL is still actively recruiting and deserves our support. The care one will get at the NIH will be world class. A win-win situation.

It is not surprising to hear the honest response about getting adequate accrual in a chemo-immunotherapy trial is more difficult these days. I have heard similar concerns from other researchers. Now that ibrutinib and idelalisib are approved and available outside of trials, many of us are no longer considering clinical trials, especially where there is a computer randomly deciding whether we get the drug of our choice. Even trials offering an option of free ibrutinib and idelalisib are enrolling more slowly.

Dr. Farooqui also shares my excitement about ABT-199. Complete responses (CR), let alone minimal residual disease (MRD) negative responses, are rare with the two approved (though that may be changing as Dr Burger has some research showing CR and MRD negative responses with ibrutinib and mAb therapy- more on this important data point later), but CR and MRD- do occur in combination trials with ABT-199. 

I keep trying to get an answer to my question that is so pertinent for me and many others: what does it mean to walk around with residual disease (or not). There is still no answer and it will only be revealed with more time and more research. Dr. Farooqui does nicely lay out the possibilities.

Soon I will be posting some great audio only interviews from ASCO 2014 with Drs. O'Brien, Byrd, and Sharman. Next month I will be reporting from both ASH 2014 and early next week from the International Conference on New Concepts in B Cell Malignancies: From molecular pathogenesis to personalized treatment but this is your last chance to see me with a goatee on camera.

I have not been home for more than a few days at a time in over a month. After next week, I will have been at six medical conference, in two continents, in 6 different cities, lecturing on five different topics from alternative medicine to gout to CLL. ASH in San Francisco, a short vacation in Yosemite and maybe a quick turn-around trip to London to speak on CLL are on tap before the years' end.

This crazy schedule needs to stop.

And it will.

My plan and commitment to you is that in the very near future my focus will narrow from teaching about a variety of medical topics to only focusing on my passion to spread the news about CLL and related B cell lymphomas. I have big plans and I will need your help and support to make them come true. More to follow soon.  (There is a hint of the exciting news to come in the interview).

Labels: , , , , , , , , , , , , ,