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Maintenance Therapy Outcomes in Follicular Lymphoma

Panelists: Ian W. Flinn, MD, PhD, Sarah Cannon Research Institute; Joshua Brody, MD, Icahn School of Medicine at Mount Sanai; Nathan H. Fowler, MD, University of Texas MD Anderson Cancer Center; John P. Leonard, MD, New York Presbyterian/Weill Cornell Medical Center; Matthew Lunning, DO, University of Nebraska Medical Center; Sonali M. Smith, MD, University of Chicago
Published: Friday, Aug 03, 2018



Transcript: 

Ian W. Flinn, MD, PhD: We’ve sort of been dancing around the maintenance questions, so maybe it’s time to tackle that directly. Actually, some of the data that worried people with the GALLIUM study were that maybe in the bendamustine patients, some who had increased events were from the maintenance portion of it. There are a couple data sets; what are your thoughts on maintenance?

Sonali M. Smith, MD: I think the concept of maintenance is really attractive in a disease where, if you can get a remission, perhaps you can maintain it for a long period of time. The challenge has been that with some of the early studies that were done—and probably the PRIMA study is the gold standard, where people got rituximab-based chemotherapy followed by maintenance rituximab or observation—showed an improved progression-free survival but no difference in overall survival. The caveat to that was that around the time that the PRIMA was published, many of us had moved toward bendamustine and rituximab.
The question was, as you already stated, what is the added value of maintenance after bendamustine as opposed to R-CHOP or R-CDP, which had been used in PRIMA? So, I think there are really 2 data sets that are coming out at this meeting and in publications that inform the concept of maintenance after bendamustine. One is the BRIGHT trial, which you know you’ve published and presented. But after the BRIGHT trial was a comparison of bendamustine plus rituximab versus R-CHOP or R-CDP, and that is where the study ended, according to the initial plan. However, a good portion of patients did receive maintenance afterward at the discretion of the investigator, and a retrospective look did not find that same type of safety signal. If anything, overall survival was essentially the same and certainly not worse, maybe even just a touch better. I think, in terms of serious toxicity, that study would say that maintenance after bendamustine plus rituximab is a reasonable option without compromising overall survival.

There’s also another study that is being done by the StiL group, which did the original BR versus R-CHOP study, as well. In that study, the MAINTAIN trial, they’re looking at 2 years versus 4 years, and I think that’s where the toxicity of rituximab maintenance beyond 2 years does begin to creep in. How much rituximab to give after rituximab-chemotherapy, especially after BR, remains an open question, but certainly the BRIGHT trial and the MAINTAIN trial would suggest that there’s no significantly increased toxicity.

Ian W. Flinn, MD, PhD: Josh, how do you approach this with your patients? I think we’ve heard from several that we haven’t really seen an improvement in overall survival for patients for a decade or more. I treated most of my patients with maintenance rituximab, in the hope that a progression-free survival would ultimately translate into an improvement in overall survival. Disappointingly, we really haven’t seen that. But there are patients for whom it clearly adds to their treatment and they benefit from it. How do you approach this?

Joshua Brody, MD: Absolutely. I think we approach it gingerly, because every patient sometimes comes both to their initial therapy and then to the question of maintenance therapy with their a priori beliefs.

We have these patients who are “more is better” patients, and we have these patients who are “less is more” patients. We have these patients who say, “I’m done with my therapy. Leave me alone, and I don’t need to be seen so frequently now.” Again, without an overall survival benefit, I don’t think I have any compulsion to give them maintenance therapy. I, like you, have a lot of optimism about it, and it was approaching common practice some years ago, and that increased somewhat after the early PRIMA data came out.

Then we have these patients who just like to come to the clinic for therapy or for otherwise. This is a little bit like rituximab plus bendamustine versus single-agent rituximab, as John’s alluding to, per patient preference, and has an important role. There’s not every opportunity for patients to have some role in the management of their care. I think it’s empowering that they have some options here. I will say, honestly, it’s a minority of our patients that do now get rituximab maintenance after rituximab plus bendamustine. But, yes, the minority are frequently self-driven. They say, “I need more therapy”.

Sonali M. Smith, MD: One of the things you brought up was long-term follow-up and what is the advantage of a PFS versus overall survival finding. With the PRIMA study showing their very long-term results, I have to be honest and say, I don’t typically give maintenance for many of my patients, for the same reasons that Josh just brought up. But the long-term follow-up of the PRIMA study, showing that at 10 years, half the patients still did not require another course of therapy after 2 years of maintenance, is something that’s compelling. Even if there’s not an overall survival advantage, not requiring other therapy for 10 years is something to really consider.

Ian W. Flinn, MD, PhD: Right. I was also taken with those data, and I think it’s an important discussion. There are clearly people that I see that just the thought of progression…even when I go through and explain it, it doesn’t necessarily change their overall survival at all. It’s just so hard for them to take; to do anything so that they can plan their life better is important.

Transcript Edited for Clarity 

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Transcript: 

Ian W. Flinn, MD, PhD: We’ve sort of been dancing around the maintenance questions, so maybe it’s time to tackle that directly. Actually, some of the data that worried people with the GALLIUM study were that maybe in the bendamustine patients, some who had increased events were from the maintenance portion of it. There are a couple data sets; what are your thoughts on maintenance?

Sonali M. Smith, MD: I think the concept of maintenance is really attractive in a disease where, if you can get a remission, perhaps you can maintain it for a long period of time. The challenge has been that with some of the early studies that were done—and probably the PRIMA study is the gold standard, where people got rituximab-based chemotherapy followed by maintenance rituximab or observation—showed an improved progression-free survival but no difference in overall survival. The caveat to that was that around the time that the PRIMA was published, many of us had moved toward bendamustine and rituximab.
The question was, as you already stated, what is the added value of maintenance after bendamustine as opposed to R-CHOP or R-CDP, which had been used in PRIMA? So, I think there are really 2 data sets that are coming out at this meeting and in publications that inform the concept of maintenance after bendamustine. One is the BRIGHT trial, which you know you’ve published and presented. But after the BRIGHT trial was a comparison of bendamustine plus rituximab versus R-CHOP or R-CDP, and that is where the study ended, according to the initial plan. However, a good portion of patients did receive maintenance afterward at the discretion of the investigator, and a retrospective look did not find that same type of safety signal. If anything, overall survival was essentially the same and certainly not worse, maybe even just a touch better. I think, in terms of serious toxicity, that study would say that maintenance after bendamustine plus rituximab is a reasonable option without compromising overall survival.

There’s also another study that is being done by the StiL group, which did the original BR versus R-CHOP study, as well. In that study, the MAINTAIN trial, they’re looking at 2 years versus 4 years, and I think that’s where the toxicity of rituximab maintenance beyond 2 years does begin to creep in. How much rituximab to give after rituximab-chemotherapy, especially after BR, remains an open question, but certainly the BRIGHT trial and the MAINTAIN trial would suggest that there’s no significantly increased toxicity.

Ian W. Flinn, MD, PhD: Josh, how do you approach this with your patients? I think we’ve heard from several that we haven’t really seen an improvement in overall survival for patients for a decade or more. I treated most of my patients with maintenance rituximab, in the hope that a progression-free survival would ultimately translate into an improvement in overall survival. Disappointingly, we really haven’t seen that. But there are patients for whom it clearly adds to their treatment and they benefit from it. How do you approach this?

Joshua Brody, MD: Absolutely. I think we approach it gingerly, because every patient sometimes comes both to their initial therapy and then to the question of maintenance therapy with their a priori beliefs.

We have these patients who are “more is better” patients, and we have these patients who are “less is more” patients. We have these patients who say, “I’m done with my therapy. Leave me alone, and I don’t need to be seen so frequently now.” Again, without an overall survival benefit, I don’t think I have any compulsion to give them maintenance therapy. I, like you, have a lot of optimism about it, and it was approaching common practice some years ago, and that increased somewhat after the early PRIMA data came out.

Then we have these patients who just like to come to the clinic for therapy or for otherwise. This is a little bit like rituximab plus bendamustine versus single-agent rituximab, as John’s alluding to, per patient preference, and has an important role. There’s not every opportunity for patients to have some role in the management of their care. I think it’s empowering that they have some options here. I will say, honestly, it’s a minority of our patients that do now get rituximab maintenance after rituximab plus bendamustine. But, yes, the minority are frequently self-driven. They say, “I need more therapy”.

Sonali M. Smith, MD: One of the things you brought up was long-term follow-up and what is the advantage of a PFS versus overall survival finding. With the PRIMA study showing their very long-term results, I have to be honest and say, I don’t typically give maintenance for many of my patients, for the same reasons that Josh just brought up. But the long-term follow-up of the PRIMA study, showing that at 10 years, half the patients still did not require another course of therapy after 2 years of maintenance, is something that’s compelling. Even if there’s not an overall survival advantage, not requiring other therapy for 10 years is something to really consider.

Ian W. Flinn, MD, PhD: Right. I was also taken with those data, and I think it’s an important discussion. There are clearly people that I see that just the thought of progression…even when I go through and explain it, it doesn’t necessarily change their overall survival at all. It’s just so hard for them to take; to do anything so that they can plan their life better is important.

Transcript Edited for Clarity 
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