[ Anglais] ASH 2017 Roundtable: CLL Research News and Updates From an Expert Panel

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Topics include: Treatments and Understanding

What’s the latest news in CLL coming out from ASH 2017? On location at the 2017 American Society of Hematology (ASH) meeting in Atlanta, Patient Power founder Andrew Schorr hosts an expert roundtable to review CLL news released at the conference and what it could mean for patients. Leading CLL specialists, Dr. William Wierda, Dr. Jennifer Brown and Dr. Anthony Mato, explore emerging research, including new data on CAR T-cell therapies, inhibitor treatments and the role of genetics.

This program is a Patient Empowerment Network program produced by Patient Power. We thank AbbVie, Inc. and Genentech for their support.

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Transcript

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:         

What's the latest in CLL, chronic lymphocytic leukemia, coming from the big convention where all the experts from around the world get together?  We're bringing you that right now. 

Hello and welcome to this Patient Empowerment Network program.  I'm Andrew Schorr.  We're on location in Atlantic, Georgia, where more than 25,000 physicians and researchers, a few of us patients have gathered in Atlantic for the American Society of Hematology medical meeting.  People come from around the world to discuss the latest, and among the topics they discuss is CLL.  I've been living with it for 21 years.  Certainly you and your loved one may well be affected by it.  You want to hear the latest, so we have some great experts with us to discuss what's coming out of this meeting and how can it inform you and your family so you get the treatment that's right for you. 

I want to introduce our expert guests.  Joining us is Dr. Anthony Mato from the Abramson Cancer Center at the University of Pennsylvania.  You're a director of the CLL program there.  Thank you so much for being with us. 

Dr. Mato:

Thanks for having me. 

Andrew Schorr:

And we have Dr. Jennifer Brown from the Dana-Farber Cancer Institute in Boston, and you're the director of the CLL program there.  Thank you so much for being with us. 

And the same, from MD Anderson, Dr. William Wierda joins us once again, and he is the section head for CLL there and also Medical Director? 

Dr. Wierda:

Yes, Medical Director. 

Andrew Schorr:

Department of Leukemia.  Thank you so much.  All right.  Let's start with you, Bill, a headline from this meeting that's meaningful for patients and families affected by CLL

Dr. Wierda:

So the big trial that's going to be presented, and it's going to be presented as a late breaker is the MURANO Study which is a trial with venetoclax (Venclexta)/rituximab (Rituxan) versus bendamustine (Treanda)/rituximab for previously treated patients with CLL.  And that's a positive trial, meaning the patients who receive the venetoclax/rituximab arm did much better in terms of their length of remission and response to treatment than patients who got what was considered at the time of the trial was designed, the standard of bendamustine/rituximab. 

So that's—that is probably the most important trial and data that we're hearing about that directly affects patients in the short term at this meeting.  And for me that trial is very important because it heralds the era of moving out of chemotherapy-based treatment and more into the small molecule inhibitor nonchemotherapy strategy. 

Andrew Schorr:

So just so people understand rituximab, which I have had, is an infused therapy although I think—have they come out with an injectable one too? 

Dr. Wierda:

There's a subcutaneous formula. 

Andrew Schorr:

So that's improving, and then an oral therapy, venetoclax. 

Dr. Wierda:

Right.

Andrew Schorr:

Jennifer Brown, how about you?  What's impressing you for this meeting for CLL patients? 

Dr. Brown:

Well, I certainly agree with Bill that the venetoclax/rituximab combination, which will probably get approved in the next six months or so, will represent a great new option for patients in relapse.  There's another what we call registration trial that's reading out, which will be less impactful in the short term but may lead to another option, and that's the DUO Trial, which paired a new PI3 kinase inhibitor.  This is a type of oral inhibitor, targeted drug similar to ibrutinib or venetoclax but a different pathway, to ofatumumab (Arzerra).  And that also found a quite significant benefit in the duration of disease control among relapsed/refractory CLL patients. 

Andrew Schorr:

So we're looking at how long can the therapy work.  In other words, how big a bang do you get for it for how long? 

Dr. Brown:

Right.

Andrew Schorr:

And how about you, Dr. Mato? 

Dr. Mato:

I would say a decade ago people in the CLL community were asking for more tools, more agents for treating patients.  Things have changed radically, and by this ASH meeting I think the headline is we have many active drugs, and over and over again we're seeing now how oncologists are learning how to combine those drugs differently.  And so I feel like one of the themes of the meeting is several presentations looking at how to incorporate novel agents into standard regimens, how to use them as a backbone to integrate other new agents, and then really begging the question, and I think this will be for future meetings, how do we decide which of these combinations are the right ones to move forward for our practices?

Andrew Schorr:

Let's start first though with an individual oral therapy.  I believe you've had a presentation on ibrutinib (Imbruvica).  So we've had that for a couple years now, a few years.  Many people are taking it.  How is it working?  It doesn't work for everybody, I know, and some people have cardio issues and maybe some other issues, so how—what's the latest? 

Dr. Mato:

So we have a presentation looking at the experience of patients treated with ibrutinib in clinical practice, and we put together a series of 391 patients who were treated mostly at academic medical centers, but there were actually some community practices that participated there asking the question are the experiences from clinical trials translated to our patients when they're receiving ibrutinib?  So we started to ask questions like what are the discontinuation rates, what are the toxicities that we're observing, are they different than what was reported in the clinical trial? 

Andrew Schorr:

Real-world story. 

Dr. Mato:

I mean that's the term that's been coined, but I feel like it's the clinical practice, the nonclinical trial story of some of the novel agents.  And what we're learning is that the outcomes from patients are excellent with ibrutinib in our practices, although there are some differences in the way the drug is being dosed, there's some difference in the toxicity profiles we're seeing, and I think the presentation itself serves as an opportunity for education as to how we can even further optimize the use of that agent. 

Andrew Schorr:

Jennifer, what about options for people where ibrutinib is not working, or they can't stay on it?  How do you feel about what you can offer people either in a trial or other medicines that are being approved or maybe have been approved for something else? 

Dr. Brown:

Well, we certainly do have a lot of options.  Usually I first try to work with people to see if we can manage the problem and issues that they're having, sometimes with a lower dose, sometimes with a short break.  Sometimes we can, but if that doesn't work, we have next-generation BTK inhibitors that are coming along that seem to have a reduction in some of the side effects, although the data are still a little bit limited compared to the data that we have with ibrutinib, so we'll need to follow that.  But certainly in my experience I have had fewer patients with, for example, the cardiac problems with some of these newer generation BTK inhibitors. 

Andrew Schorr:

Okay.

Dr. Brown:

We also have newer generation BTK inhibitors that work against people whose diseases progressed on ibrutinib, which is a whole new class of drugs that are coming into the fore that will be very beneficial for people for whom ibrutinib... 

Andrew Schorr:

…so like a second line, because ibrutinib can be used I think now, first line, right? 

Dr. Brown:

Right.

Andrew Schorr:

So now you're saying if you have someone where it's just not paying off for them you will have something else. 

Dr. Brown:

Still within the same family even, without even moving on to the next family, which is usually the venetoclax family or the Bcl-2 family.  We have good data for the effectiveness of venetoclax after ibrutinib. 

Andrew Schorr:

But we've mentioned a couple of novel agents as you call them, oral therapies, ibrutinib and venetoclax. 

Bill, you've had trials, and I think maybe at the other centers as well looking at the two drugs together.  So what's the rationale for that?  Do they go after the cancer cells in different ways? 

Dr. Wierda:

So they kill leukemia cells by different mechanisms, and so—and there's laboratory data that shows that and confirms that and we're looking at that in patients now.  The other aspect of combining things is that they don't have the same toxicity profile, so they're easier to put together, because you don't worry about making something much worse than it was with either drug by itself. 

So we have a trial that one of our faculty members presented which was a combination of ibrutinib and venetoclax for previously treated patients and for previously untreated patients.  And the purpose of that study is to give patients a defined treatment period, a defined treatment course with expectation that they will have a very deep remission at the end of that period, and that would mean that they could stop treatment and have a treatment-free period, and hopefully that would be many years like we see with chemoimmunotherapy in many cases particularly in patients who are receiving their first treatment. 

So the strategy is to get a good, deep remission initially with a defined treatment period.  We're looking at MRD at the end of that treatment. 

Andrew Schorr:

Minimal residual disease. 

Dr. Wierda:

Minimal residual disease—and to be able to stop the treatment and give them a treatment?free, treatment-free period.  So we're seeing very promising results.  We reported early results from that trial, and we're seeing a high percentage of patients who are achieving deep minimal residual disease-free remissions. 

Andrew Schorr:

And this trial or variations of it with two drugs will be at many centers? 

Dr. Wierda:

This trial is an MD Anderson trial.  We've actually finished enrollment to the untreated patient cohort.  We have plenty of clots on the—for the previously treated patients, but we've quickly filled the untreated patient cohort.  There are other trials like this that are ongoing.  There's a trial that's being done and sponsored by Pharmacyclics that's still enrolling patients.  In the UK, there's a very large study that they're opening in untreated patients with a similar combination.  So others—and then the German CLL Study Group has a large trial with multiple arms of similar combinations, so combinations of venetoclax plus a CD20 antibody or a three-drug combination with ibrutinib, venetoclax and a CD20 antibody.  So we're studying the two small molecule oral agents, ibrutinib, venetoclax together, and other groups are studying that combination with a CD20 antibody in addition. 

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Page last updated on July 30, 2018