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Choosing Therapy for Relapsed/Refractory FL

Insights From: Bruce Cheson, MD, Lombardi Comprehensive Cancer Center; Anas Younes, MD, Memorial Sloan Kettering Cancer Center
Published: Wednesday, Sep 06, 2017



Transcript:

Anas Younes, MD: At the first relapse or progression, most of us would use both a CT scan and functional imaging, like a PET scan, for the same reason as in the frontline setting: to make sure that there is no evidence of transformation. You can usually tell from the activity of the PET scan in certain areas. If there are certain lesions that have a very high SUV, then you have to do a biopsy there to rule out transformation because, again, this could guide therapy. If there’s transformation at the time of relapse, then salvage therapy plus transplant may come to mind. If there’s no transformation and you started with R-CHOP, most of us would give R-bendamustine. If you started with R-bendamustine, most of us would switch to R-CHOP.

Bruce Cheson, MD: It’s really important to look at the duration of response to upfront therapy when deciding what to use for subsequent treatments. For example, patients who have an event within 1 or 2 years of completion of therapy have a poor outcome, and there are no regimens that are specifically designed for these patients. There are clinical trials that are focusing on them. They need a different approach. For the other patients, whose relapse occurs years after that, there remains the possibility of reusing the same treatment. Although, in this day and age where we have more and more novel therapies coming down the pike, it’s unlikely you would do that. But what you recognize is, that patient population tends to respond and to respond and to respond. Eventually, they become resistant to therapy, but that’s years out. It’s the other group that progresses in 1 or 2 years that we really need to be concerned about and hopefully identify who they are before treatment.

Now, there is destined to be, hopefully in the near future, a national study focusing on that group of patients. It’s going to be for patients who received a bendamustine-based induction regimen, and for those patients who relapse within 2 years, they’re going to randomized to 1 of 3 approaches: a standard arm, most likely obinutuzumab/CHOP, or O-CHOP; obinutuzumab/lenalidomide; or obinutuzumab/idelalisib. This may change as the study comes closer to activation, but this is the concept—test standard versus investigational approaches, particularly noncytotoxic regimens.

Anas Younes, MD: The average lifespan, median survival, of patients with follicular lymphoma is now measured as approximately 18 to 20 years. That means that those patients would require multiple treatments in their lifespan. The 3 widely used regimens that are commercially available, FDA-approved, are R-CHOP or bendamustine. And when you fail both, the only drug that is currently approved is idelalisib, the PI3 kinase delta inhibitor. But outside of these treatments, and knowing that patients will still need treatments, you can’t just say, “Well, these are the only approved agents. I can’t give you any more treatment.” Many of us depend on guidelines, the like NCCN guidelines, where they incorporated active regimens that are not officially approved by the FDA for this indication but have shown good activity and a reasonable safety profile. Lenalidomide plus rituximab, which people refer to as R2 in this setting, is widely used either before or after idelalisib. There are then other active agents, mainly in context of clinical trials, that most of us would use.

Bruce Cheson, MD: The role of transplant in follicular lymphoma is, to say the least, controversial. Most feel that there is a limited role for autologous stem cell transplants. There are some studies showing prolonged progression-free survival, and maybe prolonged overall survival, but those were highly select patients who had virtually no disease at the time of the transplant. Now allogeneic transplants may have a role in patients, particularly younger patients who have few comorbidities but who have relapsed soon after induction or who are refractory to induction therapy. The use of allo transplants, or at least the displacement of them further down the road, has been engendered by the increasing number of novel targeted therapies. Allo transplants have a substantial morbidity and mortality rate. With other targeted drugs, that’s very limited. So, it’s being pushed, and pushed, and pushed further down the pike. And, in fact, with some new and exciting data looking at CAR-T cell therapy in highly refractory follicular lymphoma, the role of allogeneic transplants may even become the subject of historical value only.

Transcript Edited for Clarity
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Transcript:

Anas Younes, MD: At the first relapse or progression, most of us would use both a CT scan and functional imaging, like a PET scan, for the same reason as in the frontline setting: to make sure that there is no evidence of transformation. You can usually tell from the activity of the PET scan in certain areas. If there are certain lesions that have a very high SUV, then you have to do a biopsy there to rule out transformation because, again, this could guide therapy. If there’s transformation at the time of relapse, then salvage therapy plus transplant may come to mind. If there’s no transformation and you started with R-CHOP, most of us would give R-bendamustine. If you started with R-bendamustine, most of us would switch to R-CHOP.

Bruce Cheson, MD: It’s really important to look at the duration of response to upfront therapy when deciding what to use for subsequent treatments. For example, patients who have an event within 1 or 2 years of completion of therapy have a poor outcome, and there are no regimens that are specifically designed for these patients. There are clinical trials that are focusing on them. They need a different approach. For the other patients, whose relapse occurs years after that, there remains the possibility of reusing the same treatment. Although, in this day and age where we have more and more novel therapies coming down the pike, it’s unlikely you would do that. But what you recognize is, that patient population tends to respond and to respond and to respond. Eventually, they become resistant to therapy, but that’s years out. It’s the other group that progresses in 1 or 2 years that we really need to be concerned about and hopefully identify who they are before treatment.

Now, there is destined to be, hopefully in the near future, a national study focusing on that group of patients. It’s going to be for patients who received a bendamustine-based induction regimen, and for those patients who relapse within 2 years, they’re going to randomized to 1 of 3 approaches: a standard arm, most likely obinutuzumab/CHOP, or O-CHOP; obinutuzumab/lenalidomide; or obinutuzumab/idelalisib. This may change as the study comes closer to activation, but this is the concept—test standard versus investigational approaches, particularly noncytotoxic regimens.

Anas Younes, MD: The average lifespan, median survival, of patients with follicular lymphoma is now measured as approximately 18 to 20 years. That means that those patients would require multiple treatments in their lifespan. The 3 widely used regimens that are commercially available, FDA-approved, are R-CHOP or bendamustine. And when you fail both, the only drug that is currently approved is idelalisib, the PI3 kinase delta inhibitor. But outside of these treatments, and knowing that patients will still need treatments, you can’t just say, “Well, these are the only approved agents. I can’t give you any more treatment.” Many of us depend on guidelines, the like NCCN guidelines, where they incorporated active regimens that are not officially approved by the FDA for this indication but have shown good activity and a reasonable safety profile. Lenalidomide plus rituximab, which people refer to as R2 in this setting, is widely used either before or after idelalisib. There are then other active agents, mainly in context of clinical trials, that most of us would use.

Bruce Cheson, MD: The role of transplant in follicular lymphoma is, to say the least, controversial. Most feel that there is a limited role for autologous stem cell transplants. There are some studies showing prolonged progression-free survival, and maybe prolonged overall survival, but those were highly select patients who had virtually no disease at the time of the transplant. Now allogeneic transplants may have a role in patients, particularly younger patients who have few comorbidities but who have relapsed soon after induction or who are refractory to induction therapy. The use of allo transplants, or at least the displacement of them further down the road, has been engendered by the increasing number of novel targeted therapies. Allo transplants have a substantial morbidity and mortality rate. With other targeted drugs, that’s very limited. So, it’s being pushed, and pushed, and pushed further down the pike. And, in fact, with some new and exciting data looking at CAR-T cell therapy in highly refractory follicular lymphoma, the role of allogeneic transplants may even become the subject of historical value only.

Transcript Edited for Clarity
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