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.

ASCO 2013: The increasing numbers with Ibrutinib

As many of you know I have done very well on ibrutinib for the last year. When I started on PCI-32765 on May 7, 2012, there had been just a little more than a hundred patients who had been on the exciting new oral drug. Many of those early adapters are well known members of the CLL online community. Many are friends.

Personally, I am continuing to do great with near normal counts and no palpable nodes. CT next month in Ohio. All good. Off to Stockholm next week before EHA and just home from ASCO.

Now the community of ibrutinib users including those taking it for other B cell cancers including MCL, WM, and others now exceeds 1500 brave volunteers. Remember that the first trials were only begun in 2009. Many of those phase 1 trial patients are still on drug that tells us something about the durability of the responses, albeit in very small numbers. Still that makes the longest experience with ibrutinib something short of 4 years.

And as with many other biological treatments, the longer we stay on ibrutinib, the more responses, the more complete responses.

One of the nice problems is that when over 200 patients from the early trials were consolidated to look for those who had relapsed after more than a year on therapy, there was only a handful patients to study in more depth. Leaving aside the expected number of Richter's Transformation, about  only 1 out of 20 patients had relapsed with CLL. Most were 17p deleted but one was 11q deleted with a history of nasty auto-immune hemolytic anemia. I refer you to Dr. Sharman's nice review of the subject.

Whenever ibrutinib is approved (and hopefully that will be soon), the number of patients taking the medicine will swell. Other oral drugs may quickly follow. We will need to remain vigilant to see if rarer side effects become apparent post approval. And watch for long term surprises.

Many questions unanswered, but we have come so far in so few years.

And this is just the beginning of a new wave of targeted therapy. Ibrutinib and idelalisib and ABT-199 and GA101 are just the beginning of new wave of game changing therapies. Second and third generations of mAB and TKIs are following on their heels. We patients are needed for the trials to maintain the forward progress.

But let's celebrate the progress that we have made.

These are good times.