Finding Treatment Synergy: Combination Therapies in Development for CLL

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Topics include: Treatments

Where is research on chronic lymphocytic leukemia (CLL) combination therapies today? A panel of CLL experts including Dr. Nicole Lamanna, from Columbia University Medical Center, and Dr. Jeff Sharman, from The US Oncology Network, share compelling clinical trials results on combination therapies for CLL presented at the 2018 American Society of Hematology (ASH) annual meeting. The panel discusses the impact of biologic doublets on CLL patients long-term and who it’s currently recommended for. How are patients tolerating and responding to new treatment combinations? Tune in to find out more.

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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:

Here's my next thing I want to discuss. Combinations. We've had these combinations F and C, and then FCR or BR. Now we have this I maybe with R, but also this man received Venclexta or venetoclax, right, in a trial called the MURANO trial. And that's enabled him to stop therapy right now. That's what we had with FCR-BR. You have it, and then you're done. Hopefully, a long remission, I had 17 years, yay, very long remission. So, what about that I mean because these pills are expensive? Where are we headed with that?

Dr. Lamanna:           

This is very exciting data. And since you're part of it, thank you for participating in a clinical trial, because we can't thank patients enough for doing that, because that's how you move the field forward and answer many of these questions. Clearly, this was an update, so it wasn't that the study is new. The MURANO data was presented before, but, clearly, this was an update looking at three-year data. And so this was a relapsed trial, so patients who had already been treated for their CLL.

Andrew Schorr:       

We had FCR, six heaters, and then had Rituxan and then venetoclax.

Dr. Lamanna:           

Correct. This was looking at patients who were randomized to receive either venetoclax and rituximab versus bendamustine and rituximab. And the data was overwhelmingly favorable for the venetoclax and rituximab both in responses and progression-free survival. Then there was this sense of can patients get deep levels of response and be in not just regular routine response criteria when we think about patients in remission but also to deeper level where we detect very few residual leukemia cells? And what does that mean? How to interpret that data and then stay, as you know, you received for only 24 months the venetoclax was stopped.

So, instead of indefinitely staying on an oral therapy like ibrutinib (Imbruvica) for a prolonged period of time until you either have a side effect or you progress but having a finite period of time on an oral therapy, stopping the treatment, and then being monitored. And then having the ability if the disease comes back again, the protocol was amended to allow patients to reinitiate therapy. This is really exciting data, and, obviously, when we talk about doublets and triplets and different combinations whether or not we can utilize data like this and have patients not have to from a cost perspective or even a toxicity perspective be on indefinite oral therapy. Can we give patients a break similar to—and, again, this is different—to chemoimmunotherapy when you add FCR?

You had six months of treatment. You were done, right? You were monitored until the disease progressed again until you re-needed therapy again. Can we do that in the light of the oral therapies but maybe even get to a depth of remission that's even finer, because now technology has gotten incredibly more sensitive. Can we get better and really look at that data and inform proper decision-making about depending upon the patients disease characteristics, do we need X amount of therapy, or should we have this go on for 18 months, 24 months, 12 months and then allow people to have a drug-free period. and then can they reintroduce the same drug later on if they progress and be sensitive again to the same agents?

Dr. Sharman:     

You asked about IV, Ibrutinib in combination with venetoclax. Very exciting, provocative data that we've seen with this combination. It's got a lot of ways to appeal to you. It's an all-oral regimen. By and large, the medications are pretty well tolerated, and in terms of how they work it may be that both of them work together better than either of them apart—this thing we call synergy. There could be an enhancement that one helps the other work better than it would have if it were alone. So, there are a lot of reasons to think that this could be a particularly exciting regimen. Here's the problem.

The way drugs get developed oftentimes you can't begin to start doing clinical trials and experiments until both drugs are approved and you start putting them together. There's a big gap in the data not in terms of time. What I mean by this is I don't necessarily envision that this combination's gonna be approved by the FDA until some very important studies are done, and I worry about how long it's gonna take to get those done. It may be the FDA will squeak something through, but I don't necessarily see the route by which that's gonna happen. I think we may be in a gap of time between where we see very exciting data and when we'll be able to write a prescription for this.

Dr. Lamanna:           

Okay I'm gonna put you on the spot. Would you recommend to do this now?

Dr. Sharman:

You're going to put me on the spot. This isn't the only biologic doublet.

Dr. Lamanna:           

You're eeking out of it.

Dr. Sharman:

I'm eeking out of it. You said, well, maybe ibrutinib-rituximab. I actually want to kibosh that. I don't think you put rituximab together with ibrutinib. I think we've got two good quality studies that say not worth it. We don't know if obinutuzumab (Gazyva) adds to ibrutinib. That's likely going to be approved, and if docs were gonna do that, I could understand that. We'll have some data on that in another 18 months that will answer that question, but the biologic doublet that isn't presented at ASH—it is the elephant in the room—it's the combination of obinutuzumab with venetoclax.

Esther Schorr:          

What you previously presented but more mature.

Dr. Sharman:

Yes. We've seen data on it, but it's been in those early things. What we thought might be presented here and for some technical reasons it's not going to is a randomized, Phase III study that will almost undoubtedly read out positive. I think we know that that's gonna be the case. That's a biologic doublet that will be approved by the FDA, or at least I'm assuming it will in the relatively near term. That's a very appealing regimen, because in contrast in rituximab to ibrutinib or CD20 to Ibrutinib where I'm not really clear there's a benefit, it really does look like adding a CD20 to a Bcl-2 inhibitor could be very helpful.

Andrew Schorr:       

What's the combo? I just want to be clear on what is it, the one you're talking about?

Dr. Sharman:

You took rituximab-venetoclax, and that was a study designed for the relapsed-refractory setting. And in the frontline setting, there's going to be a trial that looks at Gazyva or obinutuzumab in combination with venetoclax. I think we'll see data on that very soon, and that's a biologic doublet that I would feel comfortable doing.

Dr. Lamanna:           

Right. It may not be we're excited about ibrutinib and venetoclax, but there are other doublets such as venetoclax and a CD20 antibody that are going to be just as exciting too. So, we have to wait for more mature data, but there are other doublets.

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 September 9, 2019