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Maintenance Therapy for Follicular Lymphoma

Panelists: Ian W. Flinn, MD, PhD, Sarah Cannon Research Institute; Matthew Lunning, DO, University of Nebraska Medical Center; John M. Pagel, MD, PhD, Swedish Cancer Institute; Pier Luigi Zinzani, MD, PhD, University of Bologna
Published: Tuesday, Aug 13, 2019



Transcript: 

Ian W. Flinn, MD, PhD: Let’s talk about maintenance. There was a period of time when rituximab maintenance, or maintenance with an antibody, was very commonplace in follicular lymphoma. At least in the US, I think the majority of people were given maintenance therapy. And we’ve gotten away, a little bit, from that. John, why is that?

John M. Pagel, MD, PhD: You’re right. The pendulum has come back to the center, and maybe it’s even swung to the other end. In fact, I think now we’re probably doing maintenance therapy in maybe a quarter of our patients; we used to do it in all our patients after induction therapy. I think we’ve learned a lot of things. In the right patient, there might be a role for maintenance, but in general, that additional therapy over a couple of years can really be associated with a lot of morbidity.

And the biggest thing we see is hypogammaglobulinemia that lasts for many, many months, if not forever, even potentially neutropenia that’s significant. And that risk for infections can be very problematic. What kind of infections are problematic in my clinic? They’re typically upper-respiratory infections, sinusitis. And you say, “Well, geez, those are things we can deal with, but they’re actually kind of nuisance infections to deal with.” That sinusitis is something that they come in, and they continue to tell us it’s a problem for them, and you know that it’s been simply because of chronic B-cell depletion. So I’m not as big a fan of it as I used to be. I think there’s a little bit of a learning curve that we have that took quite a long time.

Ian W. Flinn, MD, PhD: Yeah, but there are some patients with whom you have that discussion that we don’t know that it. We don’t think it’s going to change overall survival, but it does change progression-free survival. And having that control, I think, helps some patients, at least from a quality-of-life type of thing. Then the question is, what antibody do you use and how long? Matt, you want to tackle that?

Matthew Lunning, DO: Yeah, so…it depends on what I gave during induction. If I gave chemoimmunotherapy, often I’m giving it after….And after what ends up being a long discussion with the patient, we choose to proceed with maintenance therapy. If I gave chemoimmunotherapy, it’s every 2 months for 2 years. I have not extended beyond 2 years to 4 years, where there are some data. I think the PRIMA data still remain pretty impressive. At, I think, 10 years, over half the patients are still alive. The time needed to next therapy, which I think is a big deal when you talk about follicular lymphoma, is impressive in the maintenance arm.

But I am the first person to be having that discussion with my patient. If I start to see infections, even 1 that’s delaying therapy or affecting their quality of life—because we have to remember what maintenance is about, right? It’s to allow them to maintain their quality of life. If they’re suffering and you think it’s because you’re doing rituximab or some other monoclonal antibody maintenance, then it shouldn’t continue. It is kind of interesting because we now have other modalities like subcutaneous rituximab. So we’ve made it easier for patients to get maintenance therapies. But the pendulum is shifting, and what’s driving that is, I think, a lot of thought about what’s the endgame in these patients—including without survival.

Pier Luigi Zinzani, MD, PhD: I totally agree with my colleague. We are using maintenance, using more than 15%, 20% of the patients, because at the end of the day it’s a balance. OK, you can increase the median, the progression-free survival according to the PRIMA study. There was an update at 10 years presented 2 years ago at the ASH [American Society of Hematology Annual] Meeting & Exposition. Anyway, there is no difference in survival. And on the other side, the problem is infections—neutropenia sometimes, thrombocytopenia for several months. So it could be tough. At the end of the day, I try to use this kind of maintenance treatment only in a selected patient for whom I think could be important to reduce the risk of a relapse. But in at least 80% of patients, I avoid this kind of maintenance.

Ian W. Flinn, MD, PhD: In that 15% to 20% of patients for whom you do potentially use it, what antibody do you use?

Pier Luigi Zinzani, MD, PhD: Rituximab.

Ian W. Flinn, MD, PhD: Rituximab.

Pier Luigi Zinzani, MD, PhD: Every 2 months for 2 years.

Ian W. Flinn, MD, PhD: For 2 years. There were data from MJ Rummel and the StiL study. They were looking at 2 versus 4. What do you think of that?

Pier Luigi Zinzani, MD, PhD: If it’s quite toxic to use for 2 years, it could be a real problem to continue for the other 2 years in terms of neutropenia, risk of neutropenia, infections. I think 2 years is OK.

Ian W. Flinn, MD, PhD: There are data concerning increased mortality when using rituximab maintenance after, I think, primarily with obinutuzumab after bendamustine regimens. The data were from the BRIGHT trial, which is a randomized trial, but the patients who got maintenance therapy were not randomized, and it wasn’t worse; it was actually better. I don’t think anybody believes that it improved survival, but it gives a little bit of comfort that if you’re doing that in that setting, it’s reasonable to do that.

Transcript Edited for Clarity

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Transcript: 

Ian W. Flinn, MD, PhD: Let’s talk about maintenance. There was a period of time when rituximab maintenance, or maintenance with an antibody, was very commonplace in follicular lymphoma. At least in the US, I think the majority of people were given maintenance therapy. And we’ve gotten away, a little bit, from that. John, why is that?

John M. Pagel, MD, PhD: You’re right. The pendulum has come back to the center, and maybe it’s even swung to the other end. In fact, I think now we’re probably doing maintenance therapy in maybe a quarter of our patients; we used to do it in all our patients after induction therapy. I think we’ve learned a lot of things. In the right patient, there might be a role for maintenance, but in general, that additional therapy over a couple of years can really be associated with a lot of morbidity.

And the biggest thing we see is hypogammaglobulinemia that lasts for many, many months, if not forever, even potentially neutropenia that’s significant. And that risk for infections can be very problematic. What kind of infections are problematic in my clinic? They’re typically upper-respiratory infections, sinusitis. And you say, “Well, geez, those are things we can deal with, but they’re actually kind of nuisance infections to deal with.” That sinusitis is something that they come in, and they continue to tell us it’s a problem for them, and you know that it’s been simply because of chronic B-cell depletion. So I’m not as big a fan of it as I used to be. I think there’s a little bit of a learning curve that we have that took quite a long time.

Ian W. Flinn, MD, PhD: Yeah, but there are some patients with whom you have that discussion that we don’t know that it. We don’t think it’s going to change overall survival, but it does change progression-free survival. And having that control, I think, helps some patients, at least from a quality-of-life type of thing. Then the question is, what antibody do you use and how long? Matt, you want to tackle that?

Matthew Lunning, DO: Yeah, so…it depends on what I gave during induction. If I gave chemoimmunotherapy, often I’m giving it after….And after what ends up being a long discussion with the patient, we choose to proceed with maintenance therapy. If I gave chemoimmunotherapy, it’s every 2 months for 2 years. I have not extended beyond 2 years to 4 years, where there are some data. I think the PRIMA data still remain pretty impressive. At, I think, 10 years, over half the patients are still alive. The time needed to next therapy, which I think is a big deal when you talk about follicular lymphoma, is impressive in the maintenance arm.

But I am the first person to be having that discussion with my patient. If I start to see infections, even 1 that’s delaying therapy or affecting their quality of life—because we have to remember what maintenance is about, right? It’s to allow them to maintain their quality of life. If they’re suffering and you think it’s because you’re doing rituximab or some other monoclonal antibody maintenance, then it shouldn’t continue. It is kind of interesting because we now have other modalities like subcutaneous rituximab. So we’ve made it easier for patients to get maintenance therapies. But the pendulum is shifting, and what’s driving that is, I think, a lot of thought about what’s the endgame in these patients—including without survival.

Pier Luigi Zinzani, MD, PhD: I totally agree with my colleague. We are using maintenance, using more than 15%, 20% of the patients, because at the end of the day it’s a balance. OK, you can increase the median, the progression-free survival according to the PRIMA study. There was an update at 10 years presented 2 years ago at the ASH [American Society of Hematology Annual] Meeting & Exposition. Anyway, there is no difference in survival. And on the other side, the problem is infections—neutropenia sometimes, thrombocytopenia for several months. So it could be tough. At the end of the day, I try to use this kind of maintenance treatment only in a selected patient for whom I think could be important to reduce the risk of a relapse. But in at least 80% of patients, I avoid this kind of maintenance.

Ian W. Flinn, MD, PhD: In that 15% to 20% of patients for whom you do potentially use it, what antibody do you use?

Pier Luigi Zinzani, MD, PhD: Rituximab.

Ian W. Flinn, MD, PhD: Rituximab.

Pier Luigi Zinzani, MD, PhD: Every 2 months for 2 years.

Ian W. Flinn, MD, PhD: For 2 years. There were data from MJ Rummel and the StiL study. They were looking at 2 versus 4. What do you think of that?

Pier Luigi Zinzani, MD, PhD: If it’s quite toxic to use for 2 years, it could be a real problem to continue for the other 2 years in terms of neutropenia, risk of neutropenia, infections. I think 2 years is OK.

Ian W. Flinn, MD, PhD: There are data concerning increased mortality when using rituximab maintenance after, I think, primarily with obinutuzumab after bendamustine regimens. The data were from the BRIGHT trial, which is a randomized trial, but the patients who got maintenance therapy were not randomized, and it wasn’t worse; it was actually better. I don’t think anybody believes that it improved survival, but it gives a little bit of comfort that if you’re doing that in that setting, it’s reasonable to do that.

Transcript Edited for Clarity
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