Combination Therapy: Are Two Drugs More Effective to Combat CLL?

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Topics include: Treatments

What does the data show on the efficacy of combination therapies for chronic lymphocytic leukemia (CLL)? How do they work differently than traditional treatments to target cancer cells? CLL experts Dr. William Wierda and Dr. Anthony Mato joined us at the American Society of Hematology (ASH) 2017 annual meeting to share the latest results from clinical trial research. Tune in to find out more about CLL patient response to combination therapies.

This program is a Patient Empowerment Network program produced by PatientPower. 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:

We've mentioned a couple of novel agents as you call them, oral therapies, ibrutinib (Imbruvica) and venetoclax (Venclexta). 

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:

Exactly.  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. 

Andrew Schorr:

Okay.  So let's just talk about that.  So CD20 antibody, so I had Rituxan or rituximab.  There's also Gazyva or obinutuzumab.  Is there another one as well?  

Dr. Mato:

Ofatumumab (Arzerra).  

Andrew Schorr:

All right.  So they target a protein on the surface of the cell.  So what do you feel about that?  Do you say to people, well, you can have an infused therapy, and you're going to take this pill? But it again tries to attack the cell in two different ways, right? 

Dr. Mato:

Well, I think it's, you know, it's asking the question—first of all, the pills are incredibly active.  Regardless of which pill we're talking about, ibrutinib, venetoclax, idelalisib, these are all very active agents.  I think what we're trying to learn now is what the antibody is adding to those oral therapies.  And we've learned from years ago the work done comparing chemotherapy combinations versus chemotherapy combinations plus the antibody, the antibody improves the response rate, improves the duration of response, even makes patients live longer.  

Now we're circling back to that same question with the novel agents and trying to ask does the antibody improve the response rates?  Does it make the response last longer?  Can patients live longer because of it?  And I think right now at least with some of the novel agents we're learning there is some added activity.  The question is is it worth the benefit, and that's what these trials are hopefully going to decide over time. 

There's one presentation at the meeting that suggested the antibody probably has a little bit of activity added, but it doesn't seem to add all that much to ibrutinib when you compare it to ibrutinib by itself, but we'll see.  There are a lot of comparisons that are ongoing.  

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 28, 2018