What Progress Has Been Made in Understanding the Biology of CLL?

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Topics include: Treatments and Understanding

As a leading researcher, Dr. Kanti Rai has devoted his career to understanding and classifying CLL. Patient Power founder Andrew Schorr checks in with Dr. Rai after his return from the iwCLL conference to learn more about progress in CLL biology and how it could positively impact treatment options.

Sponsored by CLL Global Research Foundation.

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:

Hello and welcome to Patient Power.  I'm Andrew Schorr.  You know, one of the most famous specialists in CLL known around the world is Dr. Kanti Rai.  He has devoted a long career to helping us do better with CLL and hopefully working towards a cure.  So he joins us now on Patient Power once again to help us understand what the latest in CLL means for you.  Dr. Rai, welcome back to Patient Power.  

Dr. Rai:

It's a pleasure. 

Andrew Schorr:

Dr. Rai, as I said, you've been at this many years.  How far have we come in understanding the biology of CLL and, if you will, all the subtypes? 

Dr. Rai:

The biology of CLL has started to become clearer in the last 10 years, because until then in the decades before we really considered CLL as an indolent disease in which the leukemic lymphocytes did not multiply, proliferate quickly, and therefore the disease was not being treated aggressively. 

But lately we have started to understand that this is a disease with significant genetic molecular abnormalities, which render it somewhat unpredictable for clinical outcomes.  And those discoveries have led us to improved treatment, because they have enabled us to identify what we call targets.  Targeted treatments for CLL have become real, real facts and have started to help patients with this disease.  

Andrew Schorr:

Given this knowledge now, what does it mean for giving the patient the right treatment at the right time?  Are we there or not quite there yet?  

Dr. Rai:

No, we indeed have made progress to identify right patients for the right treatment.  Let me give you an example.  Dr. Michael Keating in Houston has been for two or three decades been treating patients with a combination called FCR, fludarabine (Fludara)/cyclophosphamide (Cytoxan) rituximab (Rituxan), and had demonstrated in frontline treatment that some patients can be cured and many patients achieve a good quality complete remission. 

But more recently, people have analyzed who indeed have had the better outcome with FCR and demonstrated that about just less than 30 percent of all frontline people who get treatment with CLL—FCR, if they are having unmutated IgVH genes they do poorly or less well, whereas if they have mutated IgVH gene and they also have two additional qualities of chromosome abnormalities they do not have 17p deletion and they do not have 11q deletion. 

So those three factors if they exist in the same patient, that is mutated IgVH gene, and not presence, nonpresence of 17p deletion and 11q deletion, those patients when given FCR in frontline have a very high likelihood of having the disease cured.  So this is an important observation so that we, Dr. Keating himself had found out that unmutated IgVH gene people, although they get complete remission but those remissions do not last more than a couple of years.  So now we may not offer FCR to those people who are unmutated and have 17p deletion or 11q deletions, and for them we can now concentrate and find an effective treatment which will have long?lasting remission. 

Andrew Schorr:

Dr. Rai, with the progress in approved treatments now and others that seem on the near horizon, do you feel now we have reasonable options for people even with more aggressive abnormalities, more aggressive types of CLL where options have been limited in the past? 

Dr. Rai:

Yes.  The second?generation treatments indeed are making a big, big difference for the life, longevity of our CLL patients as well as improved quality of life for those people because if they have had previous treatment like FCR or bendamustine (Treanda) rituximab or whatever and after having had a remission, now the remission is failing and more treatment becomes necessary, we did not have any proven effective treatment for those people. 

With the next generation of treatment now identified, particularly two tyrosine kinase inhibitors, one is PI3 kinase, an enzyme inhibitor, a medicine called idelalisib, and the second is Bruton's tyrosine kinase inhibitor or Btk inhibitor, which is called ibrutinib.  Both of these drugs have phenomenal activity.  They induce good quality remissions, and they are not terribly toxic so that CLL patients can tolerate it easily, tolerate both of them easily. 

Most of the records have been ibrutinib (Imbruvica) single agent and idelalisib (Zydelig) with rituximab (Rituxan).  So these are treatments which have produced good quality remission.  Big, bulky lymph nodes melt away in a matter of a few weeks after these treatments have started, and both of these treatments are orally given so that they are in the form of pills, and they do not have to have intravenous therapies.  And I am very pleased, and all the CLL patients are fully aware of these developments. 

Andrew Schorr:

Recently, you went from Long Island all the way down to Sydney Australia to attend the iwCLL meeting.  A lot was discussed there.  Were you encouraged by what you heard?  

Dr. Rai:

Yes.  At the Sydney meeting of international workshop on CLL, a number of exciting, interesting, encouraging data were presented, but the most important one I want to mention is a Bcl?2 inhibitor medicine.  Bcl?2, as many people know, is the oncogene which keeps CLL lymphocytes, leukemic lymphocytes alive and proliferating, and those—that Bcl?2 is increased in CLL, and that explains why CLL patients develop resistance to chemotherapy. 

Bcl?2 inhibitor drug is currently being tested in clinical trials, and my expectation is that within a matter of six months or 12 months the results of this medicine will be presented to the FDA and will receive okay and approval.  And this drug is as good, probably even better than idelalisib and ibrutinib, and we are very anxiously waiting for this medicine to come in clinical usage and not only limited to clinical trials. 

And I'm sure that it will happen.  The toxicities of this new drug are very little except that some people can develop tumor lysis syndrome. But once that observation was confirmed, we have been taking all safety precautions, and we have completely eliminated tumor lysis syndrome.  

Andrew Schorr:

Dr. Rai, you've been at this for so many decades.  You've devoted your life to us living with CLL.  When you look back over your career and take stock of where we are now and where it seems we're headed soon, are you encouraged? 

Dr. Rai:

Well, when I look back on my starting in CLL research it really was dismal.  We did not have any effective therapy, and now, with these developments, even what I had mentioned to you that 17p deleted people for whom we had no treatment at all excepting a few patients were salvaged with allogeneic stem cell transplant, now all of them have had excellent response with ibrutinib, even with idelalisib.  And therefore the times have so drastically changed that instead of a totally incurable disease now many of us who are working against CLL can comfortably say that this disease is reaching close to a cure, and I hope that within my lifetime we will reach that goal.  

Andrew Schorr:

Dr. Rai, on behalf of the CLL community I really want to thank you for all you've done over so many years for us.  Thank you for being with us. 

Dr. Rai:

It's always a pleasure, Andrew, to work with you, to talk to you, and I wish you all the best. 

Andrew Schorr:

Of course, we'll continue to bring you updates and insights about the latest in CLL and connect you directly with experts like Dr. Kanti Rai.  So be sure to join our community and stay updated on the latest in CLL. 

I'm Andrew Schorr.  Remember, knowledge can be the best medicine of all.  

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on November 25, 2015