Role of CAR-T in MCL


Frederick Locke, MD, discusses the role of CAR T in patients with mantle cell lymphoma, the impact it has on autologous transplant, and when transplant is recommended.

Frederick Locke, MD: Brexucabtagene autoleucel was recently approved by the FDA for the treatment of refractory mantle cell lymphoma based on the ZUMA-2 clinical trial results. That brings us to the question: What is the role of CAR [chimeric antigen receptor] T-cell therapy in mantle cell lymphoma? On label, it’s patients with refractory mantle cell lymphoma. But in all practical applications, these are patients, at least the younger and fit patients, who still likely should be getting high-dose chemotherapy regimens up front and consolidative autologous transplant if they get into remission. If they relapse following that, the treatment paradigm is generally to try a BTK inhibitor.

In theory, it’s on label to go straight to CAR T-cell therapy in the second line, but it’s been our practice to utilize BTK inhibitors for even the high-risk patients to see what kind of response they can get. A patient who gets into a complete response, a complete remission, and who does not have any high-risk features can probably ride out that remission with a BTK inhibitor for years to come. But a patient with high-risk features or a patient who doesn’t get a complete response after a few cycles, a few months, or 3 or 4 months on a BTK inhibitor is a patient who needs to be considered for CAR T-cell therapy.

What I say to referring physicians is that if you have a patient with mantle cell lymphoma who has gone through autologous transplant, was followed for years in remission, and then they relapse, send them for consideration of CAR T-cell therapy while we start a BTK inhibitor, because we want to have that CAR T-cell therapy ready to go if we need it. That’s generally how we’re utilizing it in the community, in most cases as a third-line agent after high-dose chemotherapy, autologous transplant, and a BTK inhibitor.

Is there a role for an autologous transplant in mantle cell lymphoma? There certainly is, and CAR T-cell therapy hasn’t changed that paradigm. We know that patients who undergo up-front high-dose chemotherapy, get into remission, and are consolidated after first-line treatment with an autologous transplant can maintain remissions for years to come. There are certain subsets of very high-risk patients whose outcomes may not be improved by an autologous transplant, and physicians may choose not to do an autologous transplant, but that’s still 1 of the main treatment paradigms for patients, at least here in the United States.

Older patients with comorbidities may not be fit or eligible for high-dose chemotherapy and autologous transplant, and that’s OK. CAR T-cell therapy has different sets of toxicities than transplant, and a patient who’s not eligible for autologous transplant may actually be eligible for CAR T-cell therapy based on a detailed assessment. Age should not be a factor in deciding whether a patient should be referred for CAR T-cell therapy.

Transplant still remains as something we’ll utilize in mantle cell lymphoma. That being said, there are different companies, cooperative groups, and even single centers that are designing clinical trials that would test out up-front therapy very early on with CAR T for high-risk mantle cell lymphoma patients. If we know a patient has very low chance for prolonged remission with chemotherapy and autologous transplant, can we give them CAR T earlier and improve their long-term outcomes? That’s something we’ll have to answer with clinical trials. For now, I still recommend autologous transplant if a patient is in deep remission, especially with no evidence of minimal residual disease, after frontline lead-in therapy. I would recommend a consolidative autologous transplant.

This transcript was edited for clarity.

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