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NHL Studies: CAR T Therapy, Rituximab Maintenance, & PD-L1

Panelists: John Leonard, MD, New York-Presbyterian/Weill Cornell Center for Lymphoma and Myeloma; C. Ola Landgren, MD, Memorial Sloan Kettering Cancer Center; Alexander Perl, MD, Perelman School of Medicine, University of Pennsylvania; Anas Younes, MD, Memorial Sloan Kettering Cancer Center
Published: Thursday, Dec 07, 2017



Transcript: 

John Leonard, MD: And then finally in mantle cell, our group and others, like my colleague Jia Ruan, presented some longer-term follow-up data on the combination of lenalidomide and rituximab as initial therapy in mantle cell lymphoma. A small study but a lot of careful follow-up. We demonstrated that there was MRD negativity, and then about 70% of people were still in remission 4 years later. So, interesting. Obviously, noncomparative data. And I’ll also ask you, do you think we’re reaching a point in mantle cell where we could potentially develop further these nonchemotherapy approaches as initial treatment?

Anas Younes, MD: I think we are. I think the paradigm would be, as you’ll hear from my colleague, Ola, following the mantle cell lymphomas. I think we’re going to move away from chemotherapy gradually, and we’ll use less and less stem cell transplant upfront. That’s my prediction. But they are your data. It’s very intriguing that you can achieve a 4-year progression-free survival in about 70%. Overall survival at 5 years is more than 80%. We used to think the median survival of patients is about 7 years, so this is clearly an option for some patients.

John Leonard, MD: Great. And then finally, we couldn’t leave lymphoma without talking about CART cells. We have 3 different studies: One by Neelapu, one by Abramson, one by Schuster. These are 3 different companies, 3 different drugs, approvals that either have happened or that are potentially in the works. And at every meeting, we see more and more about CAR T cells in lymphoma. Your thoughts on what’s new at ASH? Obviously, some of these abstracts we’re going to see at the meeting because it’s not yet public, but what are you going to be looking for?

Anas Younes, MD: I think the reason we see all these updates is because there’s a tremendous amount of interest in these data. People jump into an updating with the short-term follow-ups, but again, that reflects the interest in the field. So, you’re right, these 3 abstracts have been presented before. These are mainly updates. I think the one that I’m looking for is the ZUMA-1, which has now the longest follow-up. It’s about 1 year. Everybody wants to see how many will remain in CR at 1 year, because this is a good benchmark for patients with diffuse large B-cell lymphomas, the other one I think is interesting but still has short-term follow-up.

John Leonard, MD: And then, to move and to finish the lymphomas section of our program with the PRIMA Study that Gilles Salles and colleagues presented, now we have as long as 10 years of follow-up with the PRIMA study, which basically looked at rituximab maintenance after chemotherapy/rituximab as initial treatment for follicular lymphoma, and longer-term follow-up now suggesting, again, no difference in overall survival. Progression-free survival data are being presented. Toxicity long-term data are being presented. Given that a lot of people in practice, one way or another, either think about using rituximab maintenance and whether or not they actually do, a fair number of patients do receive it. What is your thought?

Anas Younes, MD: You have to put this in context. The PRIMA trial compared to R-chemotherapy versus chemotherapy without maintenance rituximab. Clearly, the data are very nice, 10-year follow-up, medium progression-free survival of about 10 years. It’s remarkable, but you have to put this in context because there’s a parallel trial from Italy, which is the full 5, which did not use maintenance. R-CHOP with no maintenance also reported 10-year follow-up and they published in JCR about a month ago with about 10-year progression-free survival. So, I think it’s confusing for the average person. I would be interested to hear your opinion, for now I reserve the maintenance for selected patients. My default is not to use maintenance for the majority of patients.

John Leonard, MD: Agreed. I talk about it with my patients, but in the absence of an overall survival benefit, the patient has a lot of flexibility. Some people really want to push being able to stay in remission. Others say, “You know, I’d rather take a break from coming in for therapy.” And the good thing for patients is that they have a choice, which is certainly nice. And then finally, in the last 15 seconds or so, you’re presenting some data using an immune checkpoint inhibitor, atezolizumab, with bendamustine and obinutuzumab, one of the first studies with immune checkpoint inhibitors in chemoimmunotherapy. Where do you think that’s going? I know it’s early but…

Anas Younes, MD: Yes, I think that’s where the field is heading right now: to incorporate these new agents that may not have overlapping toxicities with frontline regimens. So, atezolizumab is a PDL-1 antibody. The advantage of atezolizumab, I’m not interested mainly in the current administration with chemotherapy, I’m mainly interested in the adjuvant or maintenance setting. Because I think these agents may have a better chance of eradicating minimal residual disease compared to passive immune therapy, like an anti-CD20 antibody. So, I think one should focus on the MRD data.

John Leonard, MD: Great. Well, thank you, and we’ll come back with some the topics in the question-and-answer session in a few minutes.

Transcript Edited for Clarity 
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Transcript: 

John Leonard, MD: And then finally in mantle cell, our group and others, like my colleague Jia Ruan, presented some longer-term follow-up data on the combination of lenalidomide and rituximab as initial therapy in mantle cell lymphoma. A small study but a lot of careful follow-up. We demonstrated that there was MRD negativity, and then about 70% of people were still in remission 4 years later. So, interesting. Obviously, noncomparative data. And I’ll also ask you, do you think we’re reaching a point in mantle cell where we could potentially develop further these nonchemotherapy approaches as initial treatment?

Anas Younes, MD: I think we are. I think the paradigm would be, as you’ll hear from my colleague, Ola, following the mantle cell lymphomas. I think we’re going to move away from chemotherapy gradually, and we’ll use less and less stem cell transplant upfront. That’s my prediction. But they are your data. It’s very intriguing that you can achieve a 4-year progression-free survival in about 70%. Overall survival at 5 years is more than 80%. We used to think the median survival of patients is about 7 years, so this is clearly an option for some patients.

John Leonard, MD: Great. And then finally, we couldn’t leave lymphoma without talking about CART cells. We have 3 different studies: One by Neelapu, one by Abramson, one by Schuster. These are 3 different companies, 3 different drugs, approvals that either have happened or that are potentially in the works. And at every meeting, we see more and more about CAR T cells in lymphoma. Your thoughts on what’s new at ASH? Obviously, some of these abstracts we’re going to see at the meeting because it’s not yet public, but what are you going to be looking for?

Anas Younes, MD: I think the reason we see all these updates is because there’s a tremendous amount of interest in these data. People jump into an updating with the short-term follow-ups, but again, that reflects the interest in the field. So, you’re right, these 3 abstracts have been presented before. These are mainly updates. I think the one that I’m looking for is the ZUMA-1, which has now the longest follow-up. It’s about 1 year. Everybody wants to see how many will remain in CR at 1 year, because this is a good benchmark for patients with diffuse large B-cell lymphomas, the other one I think is interesting but still has short-term follow-up.

John Leonard, MD: And then, to move and to finish the lymphomas section of our program with the PRIMA Study that Gilles Salles and colleagues presented, now we have as long as 10 years of follow-up with the PRIMA study, which basically looked at rituximab maintenance after chemotherapy/rituximab as initial treatment for follicular lymphoma, and longer-term follow-up now suggesting, again, no difference in overall survival. Progression-free survival data are being presented. Toxicity long-term data are being presented. Given that a lot of people in practice, one way or another, either think about using rituximab maintenance and whether or not they actually do, a fair number of patients do receive it. What is your thought?

Anas Younes, MD: You have to put this in context. The PRIMA trial compared to R-chemotherapy versus chemotherapy without maintenance rituximab. Clearly, the data are very nice, 10-year follow-up, medium progression-free survival of about 10 years. It’s remarkable, but you have to put this in context because there’s a parallel trial from Italy, which is the full 5, which did not use maintenance. R-CHOP with no maintenance also reported 10-year follow-up and they published in JCR about a month ago with about 10-year progression-free survival. So, I think it’s confusing for the average person. I would be interested to hear your opinion, for now I reserve the maintenance for selected patients. My default is not to use maintenance for the majority of patients.

John Leonard, MD: Agreed. I talk about it with my patients, but in the absence of an overall survival benefit, the patient has a lot of flexibility. Some people really want to push being able to stay in remission. Others say, “You know, I’d rather take a break from coming in for therapy.” And the good thing for patients is that they have a choice, which is certainly nice. And then finally, in the last 15 seconds or so, you’re presenting some data using an immune checkpoint inhibitor, atezolizumab, with bendamustine and obinutuzumab, one of the first studies with immune checkpoint inhibitors in chemoimmunotherapy. Where do you think that’s going? I know it’s early but…

Anas Younes, MD: Yes, I think that’s where the field is heading right now: to incorporate these new agents that may not have overlapping toxicities with frontline regimens. So, atezolizumab is a PDL-1 antibody. The advantage of atezolizumab, I’m not interested mainly in the current administration with chemotherapy, I’m mainly interested in the adjuvant or maintenance setting. Because I think these agents may have a better chance of eradicating minimal residual disease compared to passive immune therapy, like an anti-CD20 antibody. So, I think one should focus on the MRD data.

John Leonard, MD: Great. Well, thank you, and we’ll come back with some the topics in the question-and-answer session in a few minutes.

Transcript Edited for Clarity 
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