CAR T Therapy and Durable Responses in MCL - Episode 4

Considerations for Treatment Selection in MCL

Frederick Locke, MD, explains when to choose CAR T over BTK inhibitors, patient factors to consider for CAR T cell therapy, and when BTK inhibitors are best utilized.

Frederick Locke, MD: Who is the appropriate patient to refer to be considered for CAR T-cell therapy? A patient with mantle cell lymphoma [MCL] who has relapsed following an autologous stem cell transplant should be referred for consideration of CAR [chimeric antigen receptor] T-cell therapy, at least to have that conversation. It is FDA approved for refractory mantle cell lymphoma and could in theory be given in the second line. Many patients can get through CAR T-cell therapy. This is not a treatment that only younger patients can get. We know from data with diffuse large B-cell lymphoma that patients in their 60s, 70s, and even early 80s can fare well with CAR T-cell therapy. They can make it through the acute, short-lived toxicities and come out the other side with long-term ongoing durable remissions. Age should not be a factor to not refer a patient to consider for CAR T-cell therapy. I suggest that any patient who has relapsed mantle cell lymphoma should at least have a conversation and be referred in to have a conversation with a team that could do CAR T-cell therapy. It’s always better to have established that relationship early on and be ready to go with CAR T when it’s necessary.

BTK inhibitors, including ibrutinib, work very well for mantle cell lymphoma. For patients without high-risk features, they can get remissions for many years and remain on BTK inhibitors. CAR T-cell therapy is considered early on as a second line, or sometimes with a BTK inhibitor as a bridge in patients who have those high-risk features or who don’t have a quick and deep remission with a BTK inhibitor. We’re not typically going straight to CAR T in second line. We’re always trying to get that BTK inhibitor in, but we know whom it’s not going to work for based on high-risk features. We don’t necessarily wait for them to progress. We start the ball rolling with getting authorization and getting the patient collected to CAR T-cell therapy when we know that they’re not going to have complete response or a long and ongoing durable remission. When patients relapse on a BTK inhibitor, they have very rapid progression and very high-risk features that make it difficult to get them to CAR T-cell therapy. I’d rather get the patient to CAR T while they’re still on the BTK inhibitor with a partial response or starting to progress than wait for everything to grow rapidly.

With mantle cell lymphoma, certain patients have high-risk disease features that tell us that they’re likely to progress early after frontline therapy or shortly after an autologous hematopoietic stem cell transplant. Those high-risk features include TP53 mutation, high Ki-67 proliferation index, patients with a high MIPI-c [combined MCL International Prognostic Index], and patients with blastoid variant. These are the patients who I’m not comfortable saying are going to remain in remission for years to come following an autologous transplant. In some cases, we may not even do a consolidative autologous transplant because we know that they’re very likely to relapse; in particular, the patient with TP53 mutation. That’s when I want to be thinking about CAR T early on. We always have BTK inhibitors, but even in the era of novel agents like BTK inhibitors, we believe that those patients are not going to have ongoing durable remission, so we have to have CAR T ready to go for those patients.

This transcript was edited for clarity.