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Choosing Second-Line Therapy for Relapsed/Refractory FL

Panelists: Ian W. Flinn, MD, PhD, Sarah Cannon Research Institute; Peter Martin, MD, MS, Weill Cornell Medicine; Loretta J. Nastoupil, MD, University of Texas MD Anderson Cancer Center; Grzegorz S. Nowakowski, MD, Mayo Clinic; Anas Younes, MD, Memorial Sloan Kettering Cancer Center
Published: Friday, Jan 19, 2018



Transcript: 

Ian W. Flinn, MD, PhD: Loretta, how do you tailor your next therapy, the second-line therapy, for patients who have relapsed after their first-line therapy? We have a diverse group of patients, right? We have the elderly. We’d like everyone to be the 45-year-old quarterback, but that’s usually not who we’re seeing in the clinic. Walk us through some of your considerations.

Loretta J. Nastoupil, MD: That’s a great question, and I think we struggle a lot with it because the studies in the relapsed setting are so heterogeneous in terms of the patient population. I don’t think we know what the preferred second-line or third-line approach is. What factors into that decision is, what was the response duration to their first line of therapy? And what was that first line of therapy? If you’ve had someone who had monotherapy with a CD20 antibody, I may be much less worried about that patient who’s progressing within 3 years versus someone who had chemotherapy plus a CD20 antibody.
I do think that a biopsy is critically important to know exactly what histology you’re treating. Now, do I biopsy every single patient? Not always, but I’d say probably the majority, particularly if there’s any concern for transformation. I take into account if they fall into this camp of earlier progressors. As Anas mentioned, we really don’t have a consensus across even all of us here at the table as to what the preferred approach is for those patients.

I think Carla Casulo’s data have identified the unmet need currently in follicular lymphoma, and we need to be putting all of these patients on clinical trials. However, the available trial options are so vast, how do you choose? Do you choose a nonchemotherapy approach because progressing within 24 months is maybe a suggestion that they’re not going to respond well to a second-line chemotherapy? I think the intergroup study where they’re looking at 3 different arms, including 3 different mechanisms of action, is probably the best option currently. Whether or not you intensify that therapy with a transplant, I still think, remains to be answered.

Ian W. Flinn, MD, PhD: Transplant is a controversial subject in follicular lymphoma. There’s a series of perhaps not the best-controlled studies over the last several decades, all the way back to the CUP trial. Our options are very different than they used to be in relapsed low-grade lymphoma and follicular lymphoma in particular. Peter, do you ever see a role for transplant? We can talk about autologous and allogeneic, right? Some studies show a plateau in allogeneic transplant, a survival plateau, for patients who receive that. What do you think?

Peter Martin, MD, MS: With respect to allogeneic transplant, I still have a little bit of a hard time selling that to myself, personally. And if I can’t sell it to myself, I’m not going to try to sell it to somebody else. But there probably is a role for it in some patients. For somebody who’s really young, for example, you could argue that there might be something there. With autologous transplant, as we’ve discussed, there might be a role for it in these early progressors. That’s certainly been something that has been done for a long time. For a long time, physicians have been treating early progressors with intensive therapy and autologous stem cell transplant. So, I think it’s absolutely a reasonable discussion. We know that it will likely result in a longer remission duration. That may be a very cost-effective strategy to help people do well in the long term.

Ian W. Flinn, MD, PhD: We have these new agents, and we’re going to talk about some of them in a minute. But in the past, for all forms of lymphoma, when we took someone to an autologous transplant, we used chemosensitivity as an indicator for treatment and didn’t really think that giving higher doses of chemotherapy was really going to work in patients who were chemotherapy refractory. Now we have some new agents that work by completely different mechanisms. I guess you’re not going to be in favor of giving someone one of these novel drugs and then taking them to a transplant. But biologically, it doesn’t even seem to make sense to me, right?

Peter Martin, MD, MS: Yes. It’s actually a debate that we have all the time. Not so much in follicular lymphoma, but in Hodgkin’s lymphoma where we have all of these data that say if you’re in a complete response prior to the transplant, you’re likely to do well. And I think the data from Memorial Sloan Kettering—Anas, you can comment on this maybe—is that in Hodgkin’s lymphoma, it doesn’t necessarily matter how you get to the complete response. If you get there with brentuximab vedotin and you’re not autologously transplanted, it’s still a great outcome. It may just be a marker of having the right disease.
It’s an interesting question, but I don’t think it’s necessarily appropriate to say that just because you got to a complete response because of lenalidomide or a PI3 kinase inhibitor, you’re not going to have a good response with an autologous transplant. By the same token you could argue, why would you do an autologous transplant if you had a great response with lenalidomide?

Transcript Edited for Clarity 

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Transcript: 

Ian W. Flinn, MD, PhD: Loretta, how do you tailor your next therapy, the second-line therapy, for patients who have relapsed after their first-line therapy? We have a diverse group of patients, right? We have the elderly. We’d like everyone to be the 45-year-old quarterback, but that’s usually not who we’re seeing in the clinic. Walk us through some of your considerations.

Loretta J. Nastoupil, MD: That’s a great question, and I think we struggle a lot with it because the studies in the relapsed setting are so heterogeneous in terms of the patient population. I don’t think we know what the preferred second-line or third-line approach is. What factors into that decision is, what was the response duration to their first line of therapy? And what was that first line of therapy? If you’ve had someone who had monotherapy with a CD20 antibody, I may be much less worried about that patient who’s progressing within 3 years versus someone who had chemotherapy plus a CD20 antibody.
I do think that a biopsy is critically important to know exactly what histology you’re treating. Now, do I biopsy every single patient? Not always, but I’d say probably the majority, particularly if there’s any concern for transformation. I take into account if they fall into this camp of earlier progressors. As Anas mentioned, we really don’t have a consensus across even all of us here at the table as to what the preferred approach is for those patients.

I think Carla Casulo’s data have identified the unmet need currently in follicular lymphoma, and we need to be putting all of these patients on clinical trials. However, the available trial options are so vast, how do you choose? Do you choose a nonchemotherapy approach because progressing within 24 months is maybe a suggestion that they’re not going to respond well to a second-line chemotherapy? I think the intergroup study where they’re looking at 3 different arms, including 3 different mechanisms of action, is probably the best option currently. Whether or not you intensify that therapy with a transplant, I still think, remains to be answered.

Ian W. Flinn, MD, PhD: Transplant is a controversial subject in follicular lymphoma. There’s a series of perhaps not the best-controlled studies over the last several decades, all the way back to the CUP trial. Our options are very different than they used to be in relapsed low-grade lymphoma and follicular lymphoma in particular. Peter, do you ever see a role for transplant? We can talk about autologous and allogeneic, right? Some studies show a plateau in allogeneic transplant, a survival plateau, for patients who receive that. What do you think?

Peter Martin, MD, MS: With respect to allogeneic transplant, I still have a little bit of a hard time selling that to myself, personally. And if I can’t sell it to myself, I’m not going to try to sell it to somebody else. But there probably is a role for it in some patients. For somebody who’s really young, for example, you could argue that there might be something there. With autologous transplant, as we’ve discussed, there might be a role for it in these early progressors. That’s certainly been something that has been done for a long time. For a long time, physicians have been treating early progressors with intensive therapy and autologous stem cell transplant. So, I think it’s absolutely a reasonable discussion. We know that it will likely result in a longer remission duration. That may be a very cost-effective strategy to help people do well in the long term.

Ian W. Flinn, MD, PhD: We have these new agents, and we’re going to talk about some of them in a minute. But in the past, for all forms of lymphoma, when we took someone to an autologous transplant, we used chemosensitivity as an indicator for treatment and didn’t really think that giving higher doses of chemotherapy was really going to work in patients who were chemotherapy refractory. Now we have some new agents that work by completely different mechanisms. I guess you’re not going to be in favor of giving someone one of these novel drugs and then taking them to a transplant. But biologically, it doesn’t even seem to make sense to me, right?

Peter Martin, MD, MS: Yes. It’s actually a debate that we have all the time. Not so much in follicular lymphoma, but in Hodgkin’s lymphoma where we have all of these data that say if you’re in a complete response prior to the transplant, you’re likely to do well. And I think the data from Memorial Sloan Kettering—Anas, you can comment on this maybe—is that in Hodgkin’s lymphoma, it doesn’t necessarily matter how you get to the complete response. If you get there with brentuximab vedotin and you’re not autologously transplanted, it’s still a great outcome. It may just be a marker of having the right disease.
It’s an interesting question, but I don’t think it’s necessarily appropriate to say that just because you got to a complete response because of lenalidomide or a PI3 kinase inhibitor, you’re not going to have a good response with an autologous transplant. By the same token you could argue, why would you do an autologous transplant if you had a great response with lenalidomide?

Transcript Edited for Clarity 
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