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Looking Ahead in Treating 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, Sep 10, 2019



Transcript: 

Ian W. Flinn, MD, PhD: Let’s talk about BTK [Bruton tyrosine kinase] inhibitors in follicular lymphoma. I think they’re commonly prescribed, more commonly than you would imagine in the relapsed setting in patients with that. That’s despite the data, right? Right, Matt? I mean, there are data that suggest that that’s not a good thing to do. There are also data to suggest single-arm study, but in the frontline maybe we’re getting different results, although it’s hard to interpret.

Matthew Lunning, DO: And I think that it’s taken 1 of those wins where this is non-Hodgkin lymphoma or indolent non-Hodgkin lymphoma that works, that’s approved in marginal zone. It’s approved in Waldenstrom macroglobulinemia; it’s approved in CLL [chronic lymphocytic leukemia[, SLL [small lymphocytic lymphoma]. If it’s approved in there, why wouldn’t it work in follicular lymphoma? And I think you know the data that have been shown to date that it’s not a very effective drug in follicular lymphoma, especially in the patients who are refractory to rituximab. That’s where I think the drug has toxicities to it; it has risks. And I don’t know that it has necessarily a place in follicular lymphoma speaking specifically to ibrutinib.

John M. Pagel, MD, PhD: Yeah. I might just say, I’m going to think about—I’ve said now several times—I’m definitely going to be thinking about a PI3 kinase inhibitor way before a BTK inhibitor, just because the activity is much, much greater with the PI3 kinase inhibitor.

Matthew Lunning, DO: You know, I was thinking about a scenario that’s going to come up more often now that the AUGMENT trial is positive and just going back into history and thinking about what happened when idelalisib was combined with lenalidomide. So what is the washout time that’s going to be necessary for a patient progressing on lenalidomide that you want to start a PI3 kinase inhibitor? It could be very interesting to kind of watch that, making sure that there isn’t this kind of sepsis-like syndrome that comes out over time. So, you know, spacing. It’s a theoretical thing but 1 that I don’t know we’ve necessary encountered because there probably hadn’t been a lot of second-line lenalidomide use in the prior PI3 kinase trials.

John M. Pagel, MD, PhD: That’s 1 of our major flaws of what we do: we don’t really understand sequencing because we don’t study it.

Pier Luigi Zinzani, MD, PhD: Correct.

Ian W. Flinn, MD, PhD: Well, we’ve really had a great discussion today and tackled many different topics. I think I’ll maybe give each of you a couple of minutes, a minute or 2 to talk about any closing thoughts, any take-home points from today?

Matthew Lunning, DO: I think that I’ll take the AUGMENT trial. I think it becomes a very strong option for people who are relapsed, both follicular lymphoma in the second line, and I think that’s where I’m going to see my use go up.

John M. Pagel, MD, PhD: Yeah, I think AUGMENT is exciting. We talked about RELEVANCE. I think that’s still exciting too. But a different aspect is to, again, come back to PI3 kinase inhibitors and to really understand that we’re just starting to really figure out how to use these drugs. They’re not a new class of drugs, but unfortunately it took us a long time to get where we’re at now, where we’re starting to look at the idea that we need to be doing this in a perhaps different way. Matt, you alluded to duvelisib and some alternative scheduled dosing. There are other PI3 kinases that are in development that are looking at intermittent schedules after early cytoreduction to try and avoid late T-cell or T-regulatory cell dysregulation and subsequent immune-mediated diverse events. I think we’re going to hear a lot more about PI3 kinase inhibitors. And not just hear about them but understand how to use them better, so that we will actually give a significant opportunity for our patients to benefit from that class of drugs.

Pier Luigi Zinzani, MD, PhD: Today it’s quite clear the therapeutic treatments for follicular lymphoma frontline are bendamustine plus rituximab, or you can choose bendamustine plus obinutuzumab, according to the GALLIUM study. But we were discussing before concerning the toxicity—second-line R2 [rituximab-lenalidomide] for sure and R2 [rituximab-lenalidomide] because it’s active, less toxic. And you can also apply it for aggressive follicular lymphoma because there are several data concerning that. And for the third line, we have several PI3K inhibitors. And I totally agree with Dr Pagel, because we need more data concerning the possibility to increase the activity. And at the same time we need to reduce the toxicity of the inhibitor, including an induction treatment with the regular dose for 3, 4 months. And then to use it low-dose like it maintenance consolidation treatment for 6 months, 1 year. So we need to increase the efficacy and reducing the potential toxicity.

Ian W. Flinn, MD, PhD: Yeah, we didn’t get a chance to talk about it, but there was an abstract with the MEI drug—looking at a PI3 kinase inhibitor, looking at alternative schedules in this approach—and it seems really promising. You know, I take home from this discussion that I think, for the first time in a long time, we’re starting to get a more sort of a unified approach to the treatment of follicular lymphoma.

Well, thank you for your contributions to this discussion and on behalf of our panel we thank you for joining us and we hope you found this peer exchange discussion to be useful and informative.

Transcript Edited for Clarity

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Transcript: 

Ian W. Flinn, MD, PhD: Let’s talk about BTK [Bruton tyrosine kinase] inhibitors in follicular lymphoma. I think they’re commonly prescribed, more commonly than you would imagine in the relapsed setting in patients with that. That’s despite the data, right? Right, Matt? I mean, there are data that suggest that that’s not a good thing to do. There are also data to suggest single-arm study, but in the frontline maybe we’re getting different results, although it’s hard to interpret.

Matthew Lunning, DO: And I think that it’s taken 1 of those wins where this is non-Hodgkin lymphoma or indolent non-Hodgkin lymphoma that works, that’s approved in marginal zone. It’s approved in Waldenstrom macroglobulinemia; it’s approved in CLL [chronic lymphocytic leukemia[, SLL [small lymphocytic lymphoma]. If it’s approved in there, why wouldn’t it work in follicular lymphoma? And I think you know the data that have been shown to date that it’s not a very effective drug in follicular lymphoma, especially in the patients who are refractory to rituximab. That’s where I think the drug has toxicities to it; it has risks. And I don’t know that it has necessarily a place in follicular lymphoma speaking specifically to ibrutinib.

John M. Pagel, MD, PhD: Yeah. I might just say, I’m going to think about—I’ve said now several times—I’m definitely going to be thinking about a PI3 kinase inhibitor way before a BTK inhibitor, just because the activity is much, much greater with the PI3 kinase inhibitor.

Matthew Lunning, DO: You know, I was thinking about a scenario that’s going to come up more often now that the AUGMENT trial is positive and just going back into history and thinking about what happened when idelalisib was combined with lenalidomide. So what is the washout time that’s going to be necessary for a patient progressing on lenalidomide that you want to start a PI3 kinase inhibitor? It could be very interesting to kind of watch that, making sure that there isn’t this kind of sepsis-like syndrome that comes out over time. So, you know, spacing. It’s a theoretical thing but 1 that I don’t know we’ve necessary encountered because there probably hadn’t been a lot of second-line lenalidomide use in the prior PI3 kinase trials.

John M. Pagel, MD, PhD: That’s 1 of our major flaws of what we do: we don’t really understand sequencing because we don’t study it.

Pier Luigi Zinzani, MD, PhD: Correct.

Ian W. Flinn, MD, PhD: Well, we’ve really had a great discussion today and tackled many different topics. I think I’ll maybe give each of you a couple of minutes, a minute or 2 to talk about any closing thoughts, any take-home points from today?

Matthew Lunning, DO: I think that I’ll take the AUGMENT trial. I think it becomes a very strong option for people who are relapsed, both follicular lymphoma in the second line, and I think that’s where I’m going to see my use go up.

John M. Pagel, MD, PhD: Yeah, I think AUGMENT is exciting. We talked about RELEVANCE. I think that’s still exciting too. But a different aspect is to, again, come back to PI3 kinase inhibitors and to really understand that we’re just starting to really figure out how to use these drugs. They’re not a new class of drugs, but unfortunately it took us a long time to get where we’re at now, where we’re starting to look at the idea that we need to be doing this in a perhaps different way. Matt, you alluded to duvelisib and some alternative scheduled dosing. There are other PI3 kinases that are in development that are looking at intermittent schedules after early cytoreduction to try and avoid late T-cell or T-regulatory cell dysregulation and subsequent immune-mediated diverse events. I think we’re going to hear a lot more about PI3 kinase inhibitors. And not just hear about them but understand how to use them better, so that we will actually give a significant opportunity for our patients to benefit from that class of drugs.

Pier Luigi Zinzani, MD, PhD: Today it’s quite clear the therapeutic treatments for follicular lymphoma frontline are bendamustine plus rituximab, or you can choose bendamustine plus obinutuzumab, according to the GALLIUM study. But we were discussing before concerning the toxicity—second-line R2 [rituximab-lenalidomide] for sure and R2 [rituximab-lenalidomide] because it’s active, less toxic. And you can also apply it for aggressive follicular lymphoma because there are several data concerning that. And for the third line, we have several PI3K inhibitors. And I totally agree with Dr Pagel, because we need more data concerning the possibility to increase the activity. And at the same time we need to reduce the toxicity of the inhibitor, including an induction treatment with the regular dose for 3, 4 months. And then to use it low-dose like it maintenance consolidation treatment for 6 months, 1 year. So we need to increase the efficacy and reducing the potential toxicity.

Ian W. Flinn, MD, PhD: Yeah, we didn’t get a chance to talk about it, but there was an abstract with the MEI drug—looking at a PI3 kinase inhibitor, looking at alternative schedules in this approach—and it seems really promising. You know, I take home from this discussion that I think, for the first time in a long time, we’re starting to get a more sort of a unified approach to the treatment of follicular lymphoma.

Well, thank you for your contributions to this discussion and on behalf of our panel we thank you for joining us and we hope you found this peer exchange discussion to be useful and informative.

Transcript Edited for Clarity
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