ASH 2015: Promising Combination Treatment Approaches

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Topics include: Treatment

An “embarrassment of riches” is how Dr. Andrew Zelenetz of Memorial Sloan Kettering Cancer Center describes the expanding CLL and lymphoma armamentarium.  On location at the 2015 American Society of Hematology (ASH), Dr. Zelenetz and patient advocate Carol Preston discuss the positive results of an international study—designed to improve the current standard of care—and explore promising combination treatment approaches.  Says Dr. Zelenetz, “We have the tools now to treat CLL in such a way that we can get deep remissions.”

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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.        

Carol Preston:

Hello everyone and welcome.  I'm Carol Preston, and I'm at ASH, the American Society of Hematology in Orlando, Florida.  This is the biggest, the largest blood cancer meeting on the planet, and I'm happy to be joined by Andrew Zelenetz.  Dr. Zelenetz, would you introduce yourself?  

Dr. Zelenetz:

I'm Andrew Zelenetz.  I'm the Vice Chair of the Department of Medicine at the Memorial Sloan Kettering Cancer Center.  I'm an attending physician on the lymphoma service, and I do clinical research in CLL and lymphoma.  

Carol Preston:

We just exited what was a very, very exciting news conference about several different blood cancers, including CLL.  Can you talk just a little bit from the patient's perspective about the study that you were doing?  

Dr. Zelenetz:

So the study we conducted, and I had the honor of presenting on behalf of an international group of collaborators, asked the question, could we take a standard of care treatment, that is bendamustine (Treanda) and rituximab (Rituxan), a well-recognized standard of care, and improve upon it by the addition of the drug idelalisib (Zydelig).  Idelalisib is a PI3 kinase delta inhibitor, which has substantial activity in CLL as well as follicular lymphoma, and is already approved in combination with rituximab for patients in whom chemotherapy isn't appropriate. 

But this trial was for patients for whom chemotherapy was appropriate, and so we asked the question whether if we added idelalisib to the backbone of bendamustine and rituximab, do we improve things? It was a double-blind, placebo-controlled randomized Phase III study, 416 patients in total.  There was a planned interim analysis.  This interim analysis occurred when two?thirds of the patients met their defined end point, and the independent dataset and committee met and recommended discontinuation of the study and immediate publication of the results because of overwhelming efficacy. 

Carol Preston:

So effective.  Absolutely.  Now, idelalisib is also being prescribed as Zydelig, just as an individual oral therapy.  So is it necessary to combine it with chemotherapy?  

Dr. Zelenetz:

Well, it's always a little bit difficult to do cross?trial comparisons. So the pivotal trial that led to the initial approval of idelalisib was rituximab plus idelalisib in patients who were not suitable for chemotherapy and compared to the control in that study, which was rituximab, it was overwhelmingly better.  

It's an important question whether we needed the bendamustine, but that's—you know, it was either a third arm, or it was a different study.  There could have been bendamustine-rituximab, bendamustine-rituximab plus idelalisib, rituximab plus idelalisib, and it could have been a three-arm study, but that was—that was not the exact question.  The exact question when we started was we have a standard of care, can we improve upon it?

Carol Preston:

And that doesn't mean that you wouldn't be doing a study or someone would be doing a study in the future with just idelalisib or rituximab-idelalisib. 

Dr. Zelenetz:

Absolutely.  You know, what it tells us is that this—that combining idelalisib with chemotherapy is a treatment option for patients.  But, you know, one of the things I said at the press conference is, you know, where it's now an embarrassment of riches.  We have a lot—and this is great—we have a lot of really, really good drugs for the treatment of CLL, whether it's idelalisib, whether it's duvelisib, which is not yet approved, whether it's venetoclax, which will be approved next year quite sure, whether it's ibrutinib or its cousins that are coming, or whether it's obinutuzumab (Gazyva).  You know, we have the tools now to treat CLL in such a way that we can get deep remissions, and that—where we have difficulty finding minimal residual disease, that has the potential to me to change the natural history of the disease.  And so the real…

Carol Preston:

Are you calling it a cure?  Are you saying…

Dr. Zelenetz:

Well, it has the potential for a cure.  I'm not saying we have the cure, but what I'm saying is our challenge going forward is figuring out how to best combine these very active, very good agents in a way that will potentially achieve a cure.  And, you know, so just like we had patients who were willing and able to participate in the clinical trials that were presented today, we totally depend on patients all the time to help us move the field forward.  We can come up with interesting combinations. But if patients don't enroll in the trials, we'll never know the answers.  

Carol Preston:

I got to ask this question.  You mentioned an embarrassment of riches, and it's got to be for some patients like drinking from a fire hose knowing what to do, what to ask for, and not always a hundred percent sure that their oncologist, especially maybe on—sometimes on the community level, are up to speed on everything.  So what's the message for patients? 

Dr. Zelenetz:

So there's no question that we have sequencing issues and what drug to reach to first.  And, you know, we have—with idelalisib and ibrutinib, two of the most commonly used agents, what we have are pretty equally efficacious drugs.  Ibrutinib probably has a slightly better toxicity profile, though interestingly in data that's going to be presented here the risk of discontinuation between patients on commercial ibrutinib and commercial idelalisib was identical, which was to me personally a surprise.  

Carol Preston:

So how do—how is the order discerned, or what should a patient do to be more confident about the sequencing? 

Dr. Zelenetz:

You know, I think there are circumstances in which it's very easy, you know.  Patients who are on anticoagulations, patients who already have bad—high blood pressure, patients already who have atrial fibrillation, I tend to shy away from ibrutinib.  Patients who have a history of liver disease or a history of colitis, I will certainly not start with idelalisib in those patients.  

Carol Preston:

Are there questions though that patients can ask, say, “So, doctor, we need to assess co?morbidities.” What other things are going on, as you mentioned?  

Dr. Zelenetz:

Absolutely.  You know, “Based on what you know about me, doctor, and my past medical history, are there things that help you choose one or the other?”  

Carol Preston:

Dr. Zelenetz, thank you so much.  A very, very exciting time in the area of blood cancer, targeted therapies.  Make sure you ask questions.  Your doctors need to hear from you.  I'm Carol Preston at ASH.  Thanks for watching.             

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 February 2, 2016