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Maintenance Therapy for DLBCL

Panelists: Krishna V. Komanduri, MD, Sylvester Comprehensive Cancer Center; Leo I. Gordon, MD, Robert H. Lurie Comprehensive Cancer Center; John Byrd, MD, Ohio State University; Michael Keating, MB, BS, University of Texas MD Anderson Cancer Center; John Leonard, MD, New York-Presbyterian Hospital
Published: Tuesday, Mar 07, 2017



Transcript:

Krishna V. Komanduri, MD:
Well, we’ve talked about maintenance a lot today, and I think here’s another disease in which the role of maintenance is increasingly being studied. And I’m wondering, John, if you want to talk about the REMARC study, which looked at lenalidomide and maintenance after R-CHOP in elderly patients. And there are other studies that are looking at this and reflux.

John P. Leonard, MD: So, there have been some interesting data looking at lenalidomide, also ibrutinib, in large-cell lymphoma patients in the relapse setting who appear to have the non-germinal center subtype or activated B-cell subtype, depending on the assay that you use. And those are attributable, at least in part, to pathways that are active in that particular subset of aggressive lymphoma of the activated B-cell subtype. And so, the single-agent data, just like we talked about the R-CHOP data being focused on those subtypes and those combinations, have also been more remarkable in those subtypes.

And then there have been attempts to say, “Okay, well, are there other settings where these drugs might make a difference?” And we have one example with lenalidomide, the REMARC study as you mentioned, taking older patients, over the age of 60, treated with R-CHOP in remission. So, essentially taking a population in remission and saying, “Okay, these patients have a meaningful risk of relapse. What if we give them maintenance rituximab versus observation to try to delay or prevent that relapse?” And the net of the study—it’s a large study being presented—is that the progression-free survival is improved in the group getting lenalidomide, and that’s a significant improvement.

On the other hand, overall survival is no different. And so you can look at that either way. I look forward to seeing the details of the study. Certainly, delaying relapse in an aggressive disease is often a good thing because patients are often sick when they relapse. On the other hand, you might say, “Well, you’re treating everyone versus just treating those who relapsed” and, at that point, trying lenalidomide in that situation, recognizing that despite the fact that these are elderly patients, they’re in remission. So, the relapsed rate of those patients is not 100%. One might argue if you have a group of 60+ year-old patients who finish their R-CHOP and are in complete remission, most of those patients are probably not going to relapse if they’ve made it that far and they’re in remission. I think it’ll be interesting to see how that goes. It probably will be one option that we will start to think about and discuss with our patients, and really go forward from there.

There’s interestingly another very small study in relapsed patients, patients getting second-line therapy, responding to it, suggesting that there might be a benefit. This was a nonrandomized trial, but it suggested that patients stayed in remission having been on lenalidomide maintenance longer than you might have expected with their second-line regimen without a transplant. So, there’s also, again, just another little piece of information, not rigorous in my mind, to perhaps move the needle in that direction. At this point, I would say it’s something to think about with our patients. But, obviously, the devil’s in the details. I think you have to think about what is this patient’s real risk of relapse and, therefore, how concerned are you to give them a maintenance strategy on this basis? And it also will be interesting to see, is the benefit confined to or enriched in the subset of patients that have the non-germinal center type? So, we’ll see those data.

Transcript Edited for Clarity

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Transcript:

Krishna V. Komanduri, MD:
Well, we’ve talked about maintenance a lot today, and I think here’s another disease in which the role of maintenance is increasingly being studied. And I’m wondering, John, if you want to talk about the REMARC study, which looked at lenalidomide and maintenance after R-CHOP in elderly patients. And there are other studies that are looking at this and reflux.

John P. Leonard, MD: So, there have been some interesting data looking at lenalidomide, also ibrutinib, in large-cell lymphoma patients in the relapse setting who appear to have the non-germinal center subtype or activated B-cell subtype, depending on the assay that you use. And those are attributable, at least in part, to pathways that are active in that particular subset of aggressive lymphoma of the activated B-cell subtype. And so, the single-agent data, just like we talked about the R-CHOP data being focused on those subtypes and those combinations, have also been more remarkable in those subtypes.

And then there have been attempts to say, “Okay, well, are there other settings where these drugs might make a difference?” And we have one example with lenalidomide, the REMARC study as you mentioned, taking older patients, over the age of 60, treated with R-CHOP in remission. So, essentially taking a population in remission and saying, “Okay, these patients have a meaningful risk of relapse. What if we give them maintenance rituximab versus observation to try to delay or prevent that relapse?” And the net of the study—it’s a large study being presented—is that the progression-free survival is improved in the group getting lenalidomide, and that’s a significant improvement.

On the other hand, overall survival is no different. And so you can look at that either way. I look forward to seeing the details of the study. Certainly, delaying relapse in an aggressive disease is often a good thing because patients are often sick when they relapse. On the other hand, you might say, “Well, you’re treating everyone versus just treating those who relapsed” and, at that point, trying lenalidomide in that situation, recognizing that despite the fact that these are elderly patients, they’re in remission. So, the relapsed rate of those patients is not 100%. One might argue if you have a group of 60+ year-old patients who finish their R-CHOP and are in complete remission, most of those patients are probably not going to relapse if they’ve made it that far and they’re in remission. I think it’ll be interesting to see how that goes. It probably will be one option that we will start to think about and discuss with our patients, and really go forward from there.

There’s interestingly another very small study in relapsed patients, patients getting second-line therapy, responding to it, suggesting that there might be a benefit. This was a nonrandomized trial, but it suggested that patients stayed in remission having been on lenalidomide maintenance longer than you might have expected with their second-line regimen without a transplant. So, there’s also, again, just another little piece of information, not rigorous in my mind, to perhaps move the needle in that direction. At this point, I would say it’s something to think about with our patients. But, obviously, the devil’s in the details. I think you have to think about what is this patient’s real risk of relapse and, therefore, how concerned are you to give them a maintenance strategy on this basis? And it also will be interesting to see, is the benefit confined to or enriched in the subset of patients that have the non-germinal center type? So, we’ll see those data.

Transcript Edited for Clarity
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