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Non-BTKi Agents' Role in Mantle Cell Lymphoma

Insights From: Bijal D. Shah, MD, H. Lee Moffitt Cancer Center & Research Institute; Lauren C. Pinter-Brown, MD, UCI Health; Eduardo Sotomayor, MD, GW Cancer Center
Published: Tuesday, Feb 26, 2019



Transcript:

Eduardo Sotomayor, MD:
The other combination I think that is important to mention is the combination of lenalidomide with rituximab. This is the study that has started accrual now. It has 5 years’ follow-up. So these are patients who receive induction with lenalidomide and rituximab and then they continue on lenalidomide. Some patients can stop treatment after 2 or 3 years. But the important data, at least to me, are that they are seeing some molecular responses in patients treated with what we call nonconventional chemotherapy.

So, if 20 years ago you told me that mantle cell lymphoma would be ever treated with just nonconventional chemotherapy, I would say, “No, it’s not going to happen,” Well, it’s happened. So there is a lot of hope about these combinations, the rational combination of lenalidomide/rituximab, the rational combination of ibrutinib with venetoclax as a frontline treatment for mantle cell lymphoma.

There is still going to be a role for ibrutinib with chemoimmunotherapy for a selected group of patients. I think during most of my discussion I talk about the elderly patients because that is where we are going to see mantle cell lymphoma. But there are patients who are 40 years old, 50 years old, or 60 years old who are going to be diagnosed with mantle cell lymphoma, and in those patients, yes, I want to be more aggressive trying to induce a larger duration of response because then I’m going to have time until the new discoveries. If the patients relapse, then I’m going to have more treatments to offer to these patients.

Bijal D. Shah, MD: I am very excited about the potential for CAR [chimeric antigen receptor] T-cell therapy in mantle cell lymphoma. There are ongoing trials, both within the Celgene/Juno group and within the Kite/Gilead group, asking this question: Can we improve outcomes? Given what we’ve seen in acute lymphoblastic leukemia, given what we’ve seen in diffuse large B-cell lymphoma, I‘m very encouraged, very excited. I think that we are starting to optimize the management of toxicity, so the fact that these patients are older coming in to this therapy is less of a concern for me. And I think that we have a real potential here, but we have to see what the trial data ultimately show.

Eduardo Sotomayor, MD: In terms of the new generation of anti-CD20 antibodies, some of them are more potent than the others. I think that monoclonal antibodies are going to still be part of the armamentarium, are going to add some value in some scenarios. The example is Michael Wang’s study, where anti-CD20, although it was rituximab, benefitted to ibrutinib in patients with low proliferation rate. Are the new antibodies going to improve the outcomes in patients with mantle cell lymphoma with high proliferation rate? This remains to be seen.

If someone is able to show that the new generation of anti-CD20s increase the efficacy of ibrutinib for any other targeted agent in this population with high proliferation index, then I would say, yes, there is a benefit. Perhaps, because of the binding to different epitopes, this new anti-CD20 is improving the efficacy in combination with this drug. But, at this point we need to test that in the context of clinical trial.

Lauren C. Pinter-Brown, MD: In the maintenance setting, what we do know about is monoclonal antibodies. What we don’t know about is how we might use those same maintenance monoclonal antibodies if we were able to get a deep response with other agents such as ibrutinib or venetoclax. What I mean by that is that maintenance in that setting might allow you to discontinue the small molecule drugs and reinitiate them at relapse.

Transcript edited for clarity.
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Transcript:

Eduardo Sotomayor, MD:
The other combination I think that is important to mention is the combination of lenalidomide with rituximab. This is the study that has started accrual now. It has 5 years’ follow-up. So these are patients who receive induction with lenalidomide and rituximab and then they continue on lenalidomide. Some patients can stop treatment after 2 or 3 years. But the important data, at least to me, are that they are seeing some molecular responses in patients treated with what we call nonconventional chemotherapy.

So, if 20 years ago you told me that mantle cell lymphoma would be ever treated with just nonconventional chemotherapy, I would say, “No, it’s not going to happen,” Well, it’s happened. So there is a lot of hope about these combinations, the rational combination of lenalidomide/rituximab, the rational combination of ibrutinib with venetoclax as a frontline treatment for mantle cell lymphoma.

There is still going to be a role for ibrutinib with chemoimmunotherapy for a selected group of patients. I think during most of my discussion I talk about the elderly patients because that is where we are going to see mantle cell lymphoma. But there are patients who are 40 years old, 50 years old, or 60 years old who are going to be diagnosed with mantle cell lymphoma, and in those patients, yes, I want to be more aggressive trying to induce a larger duration of response because then I’m going to have time until the new discoveries. If the patients relapse, then I’m going to have more treatments to offer to these patients.

Bijal D. Shah, MD: I am very excited about the potential for CAR [chimeric antigen receptor] T-cell therapy in mantle cell lymphoma. There are ongoing trials, both within the Celgene/Juno group and within the Kite/Gilead group, asking this question: Can we improve outcomes? Given what we’ve seen in acute lymphoblastic leukemia, given what we’ve seen in diffuse large B-cell lymphoma, I‘m very encouraged, very excited. I think that we are starting to optimize the management of toxicity, so the fact that these patients are older coming in to this therapy is less of a concern for me. And I think that we have a real potential here, but we have to see what the trial data ultimately show.

Eduardo Sotomayor, MD: In terms of the new generation of anti-CD20 antibodies, some of them are more potent than the others. I think that monoclonal antibodies are going to still be part of the armamentarium, are going to add some value in some scenarios. The example is Michael Wang’s study, where anti-CD20, although it was rituximab, benefitted to ibrutinib in patients with low proliferation rate. Are the new antibodies going to improve the outcomes in patients with mantle cell lymphoma with high proliferation rate? This remains to be seen.

If someone is able to show that the new generation of anti-CD20s increase the efficacy of ibrutinib for any other targeted agent in this population with high proliferation index, then I would say, yes, there is a benefit. Perhaps, because of the binding to different epitopes, this new anti-CD20 is improving the efficacy in combination with this drug. But, at this point we need to test that in the context of clinical trial.

Lauren C. Pinter-Brown, MD: In the maintenance setting, what we do know about is monoclonal antibodies. What we don’t know about is how we might use those same maintenance monoclonal antibodies if we were able to get a deep response with other agents such as ibrutinib or venetoclax. What I mean by that is that maintenance in that setting might allow you to discontinue the small molecule drugs and reinitiate them at relapse.

Transcript edited for clarity.
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