Saturday, May 3, 2014

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.

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6 Comments:

Anonymous Anonymous said...

Wow, fascinating stuff Brian. Like a seesaw, pressing down on one clone may lift pressure on the other. I always thought of CLL as being a "thing" that we either tamp down or kill off, but for some it sounds like a small gang of punks where if you beat up one of them, the other(s) may get ticked and come at you hard. It makes you wonder about the novel agents which all seem to leave residual clones... are those primarily subclones? Are we trading some reduction in disease now for more fierce subclone activity later? Do the novel agents have some impact on subclones when used in combination since they each have different targets? Or all they all beating up on primary clones leaving less understood subclones behind for undiscovered agents to attack?

May 3, 2014 at 1:12 PM  
Anonymous Anonymous said...

I live in the same city as my CLL specialist, and I don't have a general hematologist. I am happy to be so close, however most CLL specialists are very busy, and I have wondered if I would benefit from a second set of eyes. I am in W&W. My GP knows of my condition, but I don't see him as adding much value in CLL. Its just something for him to consider when he looks at my chart.

Do you think better to have a general hematologist in the mix?

May 3, 2014 at 1:21 PM  
Anonymous Anonymous said...

Multiple clones and an unstable genome are common in multiple myeloma and it has been found that a multi-drug combination is effective in keeping the cancer in check in a maintenance mode. I don't think there are enough different drugs yet for this to be the case in CLL. Be well, TomD

May 4, 2014 at 8:12 AM  
Blogger wayne wells said...

Brian,
This should be a mandatory viewing for every patient and doc associated with CLL patients.

I thought I was being smart in getting a Oncologist who was also a hematologist and an HSCT specialist to boot when I fired the first couple of general Oncs who were obviously ignorant of CLL. If I had stayed with her and not gone to Dr. Byrd I might not be here to be writing this. John Byrd's intimate knowledge of CLL and insight into my life threatening failure on HD-RTX helped set me on the Ibru path where I now enjoy a high quality of life and very low levels of CLL.

Looking forward to the second part and one can only guess on how TKIs may effect the critical clonal evolution question.

WWW

May 5, 2014 at 6:54 AM  
Anonymous Anonymous said...

concerning your ".. long time mantra of getting a CLL expert…", I found 2 lists from ACOR and Dr. Jeff Sharman and note that there are a scarcity of names. Though I'm sure these are not meant to be definitive or exhaustive, my question is more about the acceptability of the "non-experts and whether in ones attempt to get informed optimal care, they might be determined to have adequate experience and current knowledge or are at respected institutions where they could access the knowledge and expertise of others.

As a personal example, I'm in Florida and found five "experts" with the two closest being two hours away, yet having been sent to MD Anderson, Orlando (now the University of Florida Cancer Center), which has perhaps the top reputation in the area, I immediately felt a two hour trip was unnecessary.

But having said that, I must say that since diagnosis in March 2012 (then W & W at stage 0, now closing in on stage 1), I've felt my care has not been optimal. Initially I had arguments with my doctor as to tests ordered and protocols followed with most of my requests to deviate from them being informed by the e-guidance of Chaya Venkat, Terry Hamblin, Jeff Sharman, and the IWCLL . Though I won most of those debates I've always remained concerned because 1) of the feeling of being in an adversarial role with my doctor, 2) his tendency to minimize my worries by comparing me with patients with acute and aggressive forms, and 3) because of what feels like a minimalist approach to monitoring and care (for example if it wasn't for my own researching efforts I would never have heard about the importance of vitamin supplements and vaccinations - both those you should get if needed and those which you should stay away from.

I did initially fight to change doctors to another MDA oncologist on staff who had come highly and personally recommended and whose bio was about the only one to list Leukemia as his special area of interest - this idea was soundly rejected by the powers that be with the best reason given that the entire dept. consults with each other every week so I'd benefit from his expertise as well. But I wonder, given the CLL Expert mantra, do you think a non-expert like this doctor, with his situation and credentials, would rise to level optimally sought?

Thanks so much for your time and your expert opinion and more for your being there (especially without Chaya and Terry)

May 5, 2014 at 12:56 PM  
Blogger Jeffrey Zuckerman said...

The video take away for me was to hopefully get to a kinase inhibitor as front line treatment. Also makes me wonder what or if I have subclones?
I hope you are feeling well Doc.
Jeff

May 6, 2014 at 4:28 PM  

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