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Maintenance Therapy in Mantle Cell Lymphoma

Panelists: Alexey V. Danilov, MD, PhD, Oregon Health & Science University; Andre Goy, MD, Hackensack University Medical Center; John P. Leonard, MD, New York-Presbyterian/Weill Cornell Medical Center; John M. Pagel, MD, PhD, DSc, Swedish Medical Center Seattle and Issaquah; Stephen J. Schuster, MD, The University of Pennsylvania
Published: Tuesday, Jan 16, 2018



Transcript: 

John P. Leonard, MD: Before we end our discussion on upfront therapy, probably the most important thing that the audience needs to know relates to maintenance therapy. We have randomized trials with overall survival benefits in a couple different situations. Alexey, what are your key messages on maintenance that the audience needs to know about? Whether they have that older patient who gets something like BR, something along those lines where it is less aggressive, or the younger patient who gets a transplant. What do people need to know about maintenance in those scenarios?

Alexey V. Danilov, MD, PhD: Mantle cell lymphoma is a subtype of non-Hodgkin lymphoma where maintenance CD20 antibody therapy has been associated with an improvement in overall survival in 2 different settings. One setting is following induction chemotherapy, and that specifically refers to R-CHOP. These data were updated at the current ASH Annual Meeting. And that abstract deferred to the elderly mantle cell lymphoma study from Europe, which enrolled patients who were over 60 years old with stage 2 to 4 disease. They were randomized to R-CHOP or to FCR, followed by rituximab maintenance or not. Fludarabine and cyclophosphamide, at this point, we don’t use it for mantle cell lymphoma as an induction strategy. This is partly because of the study. It didn’t perform as well. So, following R-CHOP, the key message is that there was a benefit in 5-year overall survival, which went from 60% on the interferon arm to 80% on the rituximab arm. So, there was a very clear advantage. This showed a very clear benefit.

The second setting where data is clear is following autologous stem cell transplantation. That has been published in the New England Journal of Medicine. There’s a clear progression-free and overall survival benefit.

John, you asked me about bendamustine/rituximab. As far as I know, there is, right now, not clear data that maintenance rituximab is absolutely indicated there. The StiL MAINTAIN trial was a negative trial presented in 2017. In the trial, there was not a benefit to progression-free survival following rituximab maintenance with BR. So, I think the jury is still somewhat out there. What do you think?

John P. Leonard, MD: I found that study to be relatively underpowered. Why would maintenance work in R-CHOP and in transplant, and not after bendamustine? I’m sure one could back into an argument, but I tend to use maintenance after BR in mantle cell lymphoma.

Alexey V. Danilov, MD, PhD: And of course in other histologies, there are data.

John M. Pagel, MD, PhD, DSc: How about the length of maintenance that you deliver. How long?

John P. Leonard, MD: Well, I believe the transplant study was 3 years after transplant. And I think the other study was indefinite, until progression.

John M. Pagel, MD, PhD, DSc: I think there were many people, after more than 5 years, who were still getting maintenance rituximab.

Andre Goy, MD: We look at the pharmacoeconomic context, where we have to think about how we do this maintenance, for 2 reasons. We’re going to go beyond rituximab. There are trials looking at combining therapy with rituximab to improve maintenance, and maybe there is a great form of cellular immunotherapy. But at the same time, and for example, we look at the R-squared versus rituximab maintenance in Europe in elderly patients. In treating patients into progression for up to 7 years, in that context, we potentially have more toxicity. There’s also cost. Should the maintenance be based more on MRD? And we look a little bit at the Nordic trial, where you can convert patients very easily, preemptively, into negative PCR. I don’t think that they will have a worse survival.

Stephen J. Schuster, MD: And the Nordic study showed that. I think it’s a smart way to use maintenance therapy, rather than just everybody gets it forever.

Andre Goy, MD: I think we’re overdoing maintenance. I really do.

Stephen J. Schuster, MD: John, you were asking about MRD. That may be a way, in clinical practice, that you might want to use MRD.

Transcript Edited for Clarity 

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Transcript: 

John P. Leonard, MD: Before we end our discussion on upfront therapy, probably the most important thing that the audience needs to know relates to maintenance therapy. We have randomized trials with overall survival benefits in a couple different situations. Alexey, what are your key messages on maintenance that the audience needs to know about? Whether they have that older patient who gets something like BR, something along those lines where it is less aggressive, or the younger patient who gets a transplant. What do people need to know about maintenance in those scenarios?

Alexey V. Danilov, MD, PhD: Mantle cell lymphoma is a subtype of non-Hodgkin lymphoma where maintenance CD20 antibody therapy has been associated with an improvement in overall survival in 2 different settings. One setting is following induction chemotherapy, and that specifically refers to R-CHOP. These data were updated at the current ASH Annual Meeting. And that abstract deferred to the elderly mantle cell lymphoma study from Europe, which enrolled patients who were over 60 years old with stage 2 to 4 disease. They were randomized to R-CHOP or to FCR, followed by rituximab maintenance or not. Fludarabine and cyclophosphamide, at this point, we don’t use it for mantle cell lymphoma as an induction strategy. This is partly because of the study. It didn’t perform as well. So, following R-CHOP, the key message is that there was a benefit in 5-year overall survival, which went from 60% on the interferon arm to 80% on the rituximab arm. So, there was a very clear advantage. This showed a very clear benefit.

The second setting where data is clear is following autologous stem cell transplantation. That has been published in the New England Journal of Medicine. There’s a clear progression-free and overall survival benefit.

John, you asked me about bendamustine/rituximab. As far as I know, there is, right now, not clear data that maintenance rituximab is absolutely indicated there. The StiL MAINTAIN trial was a negative trial presented in 2017. In the trial, there was not a benefit to progression-free survival following rituximab maintenance with BR. So, I think the jury is still somewhat out there. What do you think?

John P. Leonard, MD: I found that study to be relatively underpowered. Why would maintenance work in R-CHOP and in transplant, and not after bendamustine? I’m sure one could back into an argument, but I tend to use maintenance after BR in mantle cell lymphoma.

Alexey V. Danilov, MD, PhD: And of course in other histologies, there are data.

John M. Pagel, MD, PhD, DSc: How about the length of maintenance that you deliver. How long?

John P. Leonard, MD: Well, I believe the transplant study was 3 years after transplant. And I think the other study was indefinite, until progression.

John M. Pagel, MD, PhD, DSc: I think there were many people, after more than 5 years, who were still getting maintenance rituximab.

Andre Goy, MD: We look at the pharmacoeconomic context, where we have to think about how we do this maintenance, for 2 reasons. We’re going to go beyond rituximab. There are trials looking at combining therapy with rituximab to improve maintenance, and maybe there is a great form of cellular immunotherapy. But at the same time, and for example, we look at the R-squared versus rituximab maintenance in Europe in elderly patients. In treating patients into progression for up to 7 years, in that context, we potentially have more toxicity. There’s also cost. Should the maintenance be based more on MRD? And we look a little bit at the Nordic trial, where you can convert patients very easily, preemptively, into negative PCR. I don’t think that they will have a worse survival.

Stephen J. Schuster, MD: And the Nordic study showed that. I think it’s a smart way to use maintenance therapy, rather than just everybody gets it forever.

Andre Goy, MD: I think we’re overdoing maintenance. I really do.

Stephen J. Schuster, MD: John, you were asking about MRD. That may be a way, in clinical practice, that you might want to use MRD.

Transcript Edited for Clarity 
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