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Mantle Cell Lymphoma: An Overview on Frontline Therapy

Panelists: Ian W. Flinn, MD, PhD, Sarah Cannon Research Institute; Matthew S. Davids, MD, MMSc, Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute; Brad Kahl, MD, Washington University School of Medicine; John Pagel, MD, PhD, Swedish Cancer Institute
Published: Tuesday, Aug 13, 2019



Transcript: 

Ian W. Flinn, MD, PhD: Perfect. We’re going to change now and talk about mantle cell lymphoma. Brad, like CLL [chronic lymphocytic leukemia], I think the landscape is ever-changing in mantle cell lymphoma, as well. Can you start by giving us a short overview or a 30,000-foot look at mantle cell lymphoma in terms of how you think about the initial therapy to differentiate those who are transplant candidates versus not. How do you approach that? Then, we’re going to talk about some details in the more targeted agents.

Brad Kahl, MD: A simplistic but useful way to think about mantle cell lymphoma is to think about the age and fitness of your newly diagnosed patient. There are occasional mantle cell patients who are candidates for watch-and-wait. That might be 10% or 15% of the newly diagnosed patients. That’s perfectly appropriate. The vast majority of patients need to move on to therapy at the time of diagnosis. For patients who are young, fit, and appropriate candidates for intensive strategies, that’s generally the preferred choice.

There are a number of reasonable, intensive strategy regimens that can be used. Some centers use hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone]. Some centers use R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] with alternating R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin]. Some centers use the Nordic regimen. There are a few other versions of this. Typically, once patients achieve remission, they’re consolidated with autologous stem-cell transplantation. Most of the recent data suggest median remission length in the 7-to-9-year range. There was a very nice publication from a French cooperative group about 18 months ago showing that maintenance rituximab given after the stem-cell transplant can improve the progression-free and overall survival above and beyond what I just mentioned.

That’s a standard approach for your young, fit patients. For your older patients, there’s less of a standard. I think most people have found the bendamustine/rituximab regimen to be very useful for older mantle cell patients. It’s well-tolerated. Interestingly, we haven’t seen any meaningful, long-term data for bendamustine/rituximab in mantle cell lymphoma. I think we’ll start to see some progression-free survival curves from a US Intergroup trial that we did a few years ago, and from some industry trials, such as the SHINE trial.

The one thing I will say is that all of these trials are taking substantially longer to read out than anybody anticipated. That is an indication that the patients are doing very well, because the events are coming in slowly. To make a long story short, bendamustine/rituximab is a very useful induction strategy. It’s controversial whether there is a role for maintenance rituximab after bendamustine/rituximab induction. Some of the European centers still prefer to use R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] with rituximab maintenance, which is also reasonable. Then, there are a few other spinoffs of those types of regimens, for example, the VR-CAP [bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone] regimen. In general, those sorts of strategies should get you 3 to 5 years of remission in your older patients.

Front line is relatively straightforward, although there is plenty of room for improvement. When you get into the relapsed setting, then things start to get much less clear, and the results start to diminish in terms of what you can expect, efficacy-wise.

Transcript Edited for Clarity

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Transcript: 

Ian W. Flinn, MD, PhD: Perfect. We’re going to change now and talk about mantle cell lymphoma. Brad, like CLL [chronic lymphocytic leukemia], I think the landscape is ever-changing in mantle cell lymphoma, as well. Can you start by giving us a short overview or a 30,000-foot look at mantle cell lymphoma in terms of how you think about the initial therapy to differentiate those who are transplant candidates versus not. How do you approach that? Then, we’re going to talk about some details in the more targeted agents.

Brad Kahl, MD: A simplistic but useful way to think about mantle cell lymphoma is to think about the age and fitness of your newly diagnosed patient. There are occasional mantle cell patients who are candidates for watch-and-wait. That might be 10% or 15% of the newly diagnosed patients. That’s perfectly appropriate. The vast majority of patients need to move on to therapy at the time of diagnosis. For patients who are young, fit, and appropriate candidates for intensive strategies, that’s generally the preferred choice.

There are a number of reasonable, intensive strategy regimens that can be used. Some centers use hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone]. Some centers use R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] with alternating R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin]. Some centers use the Nordic regimen. There are a few other versions of this. Typically, once patients achieve remission, they’re consolidated with autologous stem-cell transplantation. Most of the recent data suggest median remission length in the 7-to-9-year range. There was a very nice publication from a French cooperative group about 18 months ago showing that maintenance rituximab given after the stem-cell transplant can improve the progression-free and overall survival above and beyond what I just mentioned.

That’s a standard approach for your young, fit patients. For your older patients, there’s less of a standard. I think most people have found the bendamustine/rituximab regimen to be very useful for older mantle cell patients. It’s well-tolerated. Interestingly, we haven’t seen any meaningful, long-term data for bendamustine/rituximab in mantle cell lymphoma. I think we’ll start to see some progression-free survival curves from a US Intergroup trial that we did a few years ago, and from some industry trials, such as the SHINE trial.

The one thing I will say is that all of these trials are taking substantially longer to read out than anybody anticipated. That is an indication that the patients are doing very well, because the events are coming in slowly. To make a long story short, bendamustine/rituximab is a very useful induction strategy. It’s controversial whether there is a role for maintenance rituximab after bendamustine/rituximab induction. Some of the European centers still prefer to use R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] with rituximab maintenance, which is also reasonable. Then, there are a few other spinoffs of those types of regimens, for example, the VR-CAP [bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone] regimen. In general, those sorts of strategies should get you 3 to 5 years of remission in your older patients.

Front line is relatively straightforward, although there is plenty of room for improvement. When you get into the relapsed setting, then things start to get much less clear, and the results start to diminish in terms of what you can expect, efficacy-wise.

Transcript Edited for Clarity
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