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New Data for Mantle Cell Lymphoma

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: Great. So, now I want to move to mantle cell lymphoma. We have some interesting data. We have a new drug approval in mantle cell lymphoma, which we’ll get to in a second. But first, there have been a couple of studies looking at maintenance rituximab in various situations in mantle cell lymphoma. The French group, Le Gouill, have looked at the idea of maintenance rituximab after an auto transplant in mantle cell lymphoma. And this was an interesting subset analysis where most of the patients were treated with R-DHAP as a second-line therapy, or I should say as part of that therapy, before transplant. But a number of the patients for a variety of reasons received oxaliplatin. And it turns out that there were some interesting results. The group that got oxaliplatin seemed to do better, which is not something I could say that I would have expected. But your thoughts on this study?

Anas Younes, MD: It’s very interesting. So, I agree with you. Like we used to think platinums are the same. If someone, let’s say, failed DHAP, I would not treat them with ICE in pretransplant setting. But as you know from the CORAL studies, there are data that suggest that if they fail ICE, you can salvage them with DHAP, about 30%, which is against what everybody would have thought. I think the platinums may not be created equal, but it’s just not the platinum itself. There are other things with these platinum compounds. But yes, it’s interesting because they did not specify the type of platinum needed in the salvage regimen, they just said platinum-based regimen. The majority got the DHAP, some got ICE, and some got the oxaliplatin. Actually, the smallest subgroup received the oxaliplatin. So, in the subset analysis, it turned out that if you received the oxaliplatin, you did better in terms of PFS and overall survival, which is interesting. So, I think this is practice changing. Even though small numbers, you have to give the patient the benefit of the doubt, and I think most of us would now use an oxaliplatin-based regimen in the frontline setting. How do you interpret that?

John Leonard, MD: Yes, as I recall, it was about 35 to 40 patients, so it’s a small thing. I’d like to study it a little bit more, but I think it’s certainly a reasonable thing. There’s no big downside using the oxaliplatin in the big picture clinically, so it’s certainly worth considering. So, we’ve now recently had the approval of acalabrutinib, a new BTK, or Bruton’s tyrosine kinase inhibitor, in mantle cell. And we have a study, really the pivotal study, being presented and updated at the meeting by Michael Wang and colleagues. So, your thoughts on this drug and where it fits in mantle cell lymphoma therapy?

Anas Younes, MD: Those are new data, so this has not been presented before, but the drug was approved about a month ago. I think the paper may be in press somewhere. But it’s interesting. About 100-something patients with relapsed mantle cell lymphoma were treated with a second-generation BTK inhibitor, which is more selective. So, we don’t expect it to be more effective because it binds to the same binding site as ibrutinib, but we expect it to be more safe and probably with less side effects.

So, response rates, again here it’s very impressive. About 80% had an overall response rate with a 40% CR rate. Now face value you can think, “Oh, this is more effective than ibrutinib because the CR rate is higher.” One needs to be careful because they use different response criteria. They use the new modified Lugano criteria where all the ibrutinib use the Cheson criteria. If you compare them head-to-head, there’s really not much of a difference. Maybe a few percentage differences, but it’s certainly an interesting agent that needs to be looked at with a long-term follow-up.

John Leonard, MD: Great.

Transcript Edited for Clarity 
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Transcript: 

John Leonard, MD: Great. So, now I want to move to mantle cell lymphoma. We have some interesting data. We have a new drug approval in mantle cell lymphoma, which we’ll get to in a second. But first, there have been a couple of studies looking at maintenance rituximab in various situations in mantle cell lymphoma. The French group, Le Gouill, have looked at the idea of maintenance rituximab after an auto transplant in mantle cell lymphoma. And this was an interesting subset analysis where most of the patients were treated with R-DHAP as a second-line therapy, or I should say as part of that therapy, before transplant. But a number of the patients for a variety of reasons received oxaliplatin. And it turns out that there were some interesting results. The group that got oxaliplatin seemed to do better, which is not something I could say that I would have expected. But your thoughts on this study?

Anas Younes, MD: It’s very interesting. So, I agree with you. Like we used to think platinums are the same. If someone, let’s say, failed DHAP, I would not treat them with ICE in pretransplant setting. But as you know from the CORAL studies, there are data that suggest that if they fail ICE, you can salvage them with DHAP, about 30%, which is against what everybody would have thought. I think the platinums may not be created equal, but it’s just not the platinum itself. There are other things with these platinum compounds. But yes, it’s interesting because they did not specify the type of platinum needed in the salvage regimen, they just said platinum-based regimen. The majority got the DHAP, some got ICE, and some got the oxaliplatin. Actually, the smallest subgroup received the oxaliplatin. So, in the subset analysis, it turned out that if you received the oxaliplatin, you did better in terms of PFS and overall survival, which is interesting. So, I think this is practice changing. Even though small numbers, you have to give the patient the benefit of the doubt, and I think most of us would now use an oxaliplatin-based regimen in the frontline setting. How do you interpret that?

John Leonard, MD: Yes, as I recall, it was about 35 to 40 patients, so it’s a small thing. I’d like to study it a little bit more, but I think it’s certainly a reasonable thing. There’s no big downside using the oxaliplatin in the big picture clinically, so it’s certainly worth considering. So, we’ve now recently had the approval of acalabrutinib, a new BTK, or Bruton’s tyrosine kinase inhibitor, in mantle cell. And we have a study, really the pivotal study, being presented and updated at the meeting by Michael Wang and colleagues. So, your thoughts on this drug and where it fits in mantle cell lymphoma therapy?

Anas Younes, MD: Those are new data, so this has not been presented before, but the drug was approved about a month ago. I think the paper may be in press somewhere. But it’s interesting. About 100-something patients with relapsed mantle cell lymphoma were treated with a second-generation BTK inhibitor, which is more selective. So, we don’t expect it to be more effective because it binds to the same binding site as ibrutinib, but we expect it to be more safe and probably with less side effects.

So, response rates, again here it’s very impressive. About 80% had an overall response rate with a 40% CR rate. Now face value you can think, “Oh, this is more effective than ibrutinib because the CR rate is higher.” One needs to be careful because they use different response criteria. They use the new modified Lugano criteria where all the ibrutinib use the Cheson criteria. If you compare them head-to-head, there’s really not much of a difference. Maybe a few percentage differences, but it’s certainly an interesting agent that needs to be looked at with a long-term follow-up.

John Leonard, MD: Great.

Transcript Edited for Clarity 
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