The Evolving CLL Treatment Landscape

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Topics include: Treatment

Patient Power Founder and host, Andrew Schorr, interviews CLL expert Dr. Richard Furman to discuss the evolving CLL treatment landscape, including the introduction of venetoclax (Venclexta) to the CLL armamentarium.  

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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 in San Diego.  We're joined by Dr. Richard Furman from Weill Cornell Medical College in New York City, a leading expert in CLL, to really discuss in light of a new drug approval in CLL, where do we go from here?  What does it mean for the CLL community as we try to have more patients, including, of course, people with the most serious forms of CLL or complications from CLL, do better?  Dr. Furman, welcome to back to Patient Power. 

Dr. Furman:

Thank you very much for having me.  

Andrew Schorr:

So now we have a new drug approved, a powerful new drug, and you have others that you've had in approvals over the last year or so.  You have drugs that are injected and pills we take.  Now, where are we now in trying to help more people with the addition of venetoclax (Venclexta)?  

Dr. Furman:

So venetoclax is just an additional tool for physicians to use, and it provides a very effective and extremely well tolerated medication for the treatment of patients with CLL.  What really is so important about the current approval for venetoclax is that the original trials were actually plagued by two deaths due to tumor lysis syndrome.  What I really think is very important for everyone to understand is the methodology or the process for administering the pills back then was very different than what we do now. 

And we currently do what's called a ramp?up dose schedule where you start off at 20 milligrams then go to 50, 100, 200 and 400, basically a week at that time as long as you don't show any evidence of having tumor lysis on your laboratory values.  And since this has been instituted, we've actually not had any cases of clinically significant tumor lysis.  So some patients have had laboratory abnormalities consistent with tumor lysis, but none of them met the criteria for being clinically significant. 

So we're now, you know, basically have made venetoclax—or figured out how to use venetoclax, which is a highly effective tool, safely.  And so it now joins the ranks of ibrutinib (Imbruvica) and idelalisib (Zydelig) as something that really will have a tremendous hopefully in the longevity of CLL patients. 

Andrew Schorr:

So the question is, and we've talked about this at some of your medical conferences, is combining an agent with another one, you get a synergistic effect, and would that be important for some patients? 

Dr. Furman:

So I think the most important data to look at is actually the ibrutinib 1102 data.  So this is the first Phase II study that we did with ibrutinib, and it started over about four years ago. And we treated 31 patients who were treatment?naive who needed therapy and were over the age of 65, with ibrutinib as their first treatment.  So [this was] a group of patients who needed therapy, and when they got ibrutinib as their first therapy actually only one patient has progressed out of those 31 patients while on ibrutinib. 

And this one patient was a 17p-deleted patient who developed a Richter's syndrome at month 8.  So arguably the Richter's was there before the treatment began and was just unmasked by the ibrutinib.  So in essence, if you aren't 17p, and I think the same is probably true for 11q as well as some other genetic lesions, and you get ibrutinib when you need treatment based on the standard criteria, the current data suggest that that's all you need.  So these are a group of patients who don't need anything else. 

Now, with that being said, we have data at least with ibrutinib plus rituximab and ibrutinib plus bendamustine (Treanda)-rituximab that really indicate that the chemotherapy and the immunotherapy don't enhance the outcome of patients who are receiving ibrutinib.  And I think that that's the overwhelming, most important piece of information for everyone to remember so that even the combination chemotherapy plus ibrutinib is no better than ibrutinib alone.  And so there's no need to assume excess risk. 

With that being said, there are small groups of patients like the 17p-deleted patients, the 11q deleted patients or the NOTCH1-mutated patients who have a particularly high risk of developing a transformation or genomic instability that might lead to them developing a mutation that would make them resistant to ibrutinib.  These patients may derive benefit from being put into a complete response quicker, and just the idea of removing the number of cells that are present as quickly as possible diminishes the chance of having one of these secondary hits occur that gives rises to either a Richter's or a resistance—or a mutation that causes resistance to ibrutinib. 

And so that's where venetoclax really might be so helpful, because it really does induce very deep remissions very quickly.  And so in that population of patients there really does seem to be a potential benefit of adding venetoclax to ibrutinib. 

Andrew Schorr:

So do you think the bottom line of where we are now is you have more tools, if you will, is that a wider array of CLL patients, whether they've been previously treated or they're diagnosed with the more aggressive form of CLL, that you have something for them to give them hope?  

Dr. Furman:

Absolutely.  I mean I think, you know, ibrutinib and idelalisib are wonderful agents, and I think venetoclax is just an additional agent to that armamentarium.  The thing that's I think important to keep in mind is the data for venetoclax is going to evolve over time, so we are in a position now where we're having what are called MRD?negative partial responses. 

So typically partial responses should be, you know, patients with persistent lymphadenopathy and obviously some bone marrow involvement or what?not. But what we're finding with venetoclax is patients are having lymph node sizes, you know, two to three centimeters in size and aren't having any evidence of CLL in the peripheral blood or the bone marrow.  So these MRD?negative partial responders really are doing wonderfully.  And, in fact, the MRD negativity rate is more predictive than the iwCLL response, or the partial response designation. 

So right now the data, because of how it was collected, not considering that, is really going to be representative of the true potential of venetoclax. And I think that what we'll find is that the PFS, the progression?free survival, of these patients who just have partial responses will be quite long, and that's really the important piece of information for the patients.  And I think that that's information that will evolve over the next year or two, and subsequent studies will include this whole idea about potentially being MRD negative and still being in a partial response. 

Andrew Schorr:

Right.  So, of course, the bottom line for any of us living with CLL is how do we feel.  

Dr. Furman:

Right. 

Andrew Schorr: 

We can do what we want to do with our lives, and, you know, you may see CLL in our blood or in our bone marrow, but if it's not affecting us greatly, we're doing well. 

Dr. Furman:

But just to I think clarify though, the lymph nodes in these patients who are MRD negative and they have a partial response are probably just scar or probably just other inflammatory cells and not CLL.  So I think these are a group of patients who might be cleared of their disease even though they're only in a partial response.  And so it really makes it—you know, I think it basically underestimates how wonderful the data really is. 

Andrew Schorr:

Wow.  Well, of course, we cover your big medical meetings that you have and I know when we get to ASH in December of 2016 we'll hear even more.  Dr. Richard Furman, I want to thank you for your leadership in research and working with your colleagues around the world to help move this forward for us.  And I want to thank you for being with us to help us understand how adding a new drug and the ongoing studies and maybe understanding assessment criteria, like what you were just talking about, can help us really know the value of what we have and where we're headed.  Thanks for being with us, Dr. Furman.  

Dr. Furman:

My pleasure. 

Andrew Schorr:

Okay.  Andrew Schorr with an update from a leading investigator in New York City, Dr. Richard Furman. 

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 April 26, 2016