CAR T Therapy and Durable Responses in MCL

Frederick Locke, MD: Historically, treatment of patients with relapsed or refractory mantle cell lymphoma [MCL] following frontline therapy and consolidative autologous transplant consisted of combinations of chemotherapy, several different regimens, or more novel agents, including BTK inhibitors, such as ibrutinib, zanubrutinib, and acalabrutinib. There has also been some success with proteasome inhibitors like bortezomib and immunomodulators like lenalidomide. All these agents can lead to remissions in patients with relapsed/refractory mantle cell lymphoma. In fact, the BTK inhibitors, like ibrutinib, have been very successful for putting patients into remission.

It is clear that patients with high-risk features have much more opportunity for durable and ongoing remission. Patients with mantle cell lymphoma who have high-risk features, including patients with blastoid variant mantle cell lymphoma, patients with TP53 mutations or deletions, patients with a high MIPI [MCL International Prognostic Index]—zeroing in on patients who have a high MIPI-c [combined MIPI] score that takes a count of over 30% in the Ki-67 index—are the patients who have very high risk. Even BTK inhibitors like ibrutinib don’t do a great job of keeping those patients in remission for a prolonged period of time. Combination chemotherapy regimens have been used. Fludarabine is an agent that has been used in refractory mantle cell lymphoma and some other chemotherapeutic agents. Patients with high-risk features generally fare poorly in the long term, even with these more novel agents.

This transcript was edited for clarity.