CAR T-Cell Therapy for Mantle-Cell Lymphoma

Chimeric antigen receptor (CAR) T-cell immunotherapy provides an important option for relapsed or refractory mantle-cell lymphoma (MCL). Investigators now report a multicenter, industry-sponsored, phase 1 study of lisocabtagene maraleucel (liso-cel) in patients whose MCL had progressed after two or more lines of therapy, including an anti-CD20 agent, an alkylator, and a Bruton tyrosine kinase inhibitor. Bridging therapy was permitted after leukapheresis; patients received lymphodepleting fludarabine plus cyclophosphamide for 3 days and then liso-cel infusions 2 to 7 days later (total dose, 50 or 100 x 10⁶ cells). Retreatment with liso-cel was permitted for patients who relapsed after complete remission.

Of the 104 patients who underwent leukapheresis, 88 received liso-cel (82 at the 100 x 10⁶ dose); 9 patients died before infusion, 3 did not meet eligibility criteria, and 4 received a nonconforming CAR T-cell product. Among 83 evaluable patients, the overall response rate was 83.1%, with complete remission achieved in 72.3%, including 11 of 19 with TP53 mutations, 17 of 27 with blastoid variant, and 6 of 7 with central nervous system (CNS) MCL. During a median follow-up of 23.5 months, the median progression-free survival was 15.3 months and overall survival was 18.2 months. Cytokine release syndrome occurred in 61% of patients (all grade 1 or 2 aside from one grade 4 event) and neurotoxicity in 31%, with seven (8%) grade-3 events and one (1%) grade 4. There were three treatment-related deaths, two from infections and one from tumor lysis syndrome. Seven patients died of COVID-19, with one considered treatment-emergent.