BCMA-directed CAR T-cell therapy in patients with multiple myeloma and CNS involvement
Mahmoud Gaballa, Omar Castañeda Puglianini, Adam D. Cohen, Dan T. Vogl, Alfred Chung, Christopher J. Ferreri, Peter M. Voorhees, Doris K. Hansen, Krina K. Patel
Abstract
ABSTRACT: We investigated B-cell maturation antigen-directed chimeric antigen receptor T-cell (CAR-T) therapy in patients with relapsed or refractory multiple myeloma (MM) and central nervous system (CNS) involvement. Ten patients received either idecabtagene vicleucel (n = 6) or ciltacabtagene autoleucel (n = 4), where brain/cranial nerve and/or spinal cord involvement/leptomeningeal disease were evident on either magnetic resonance imaging (100%) and/or cerebrospinal fluid (40%). Eight patients had their CNS diagnosis before CAR-T therapy, and two were diagnosed within 14 days post-infusion. Seven received CNS-directed therapy during bridging before CAR-T therapy. There were no excess toxicities: no cytokine release syndrome grade ≥3; 10% immune effector cell-associated neurotoxicity syndrome (ICANS) grade 3; and no ICANS grade 4. Two patients experienced delayed but treatable neurotoxicity, with no reported parkinsonian side effects. The best overall response rate was 80% (≥70% very good partial response) and a 100% CNS response. With a median follow-up of 381 days, patients with CNS myeloma diagnosed before CAR-T therapy (n = 8) had a median overall survival and progression-free survival (PFS) of 13.3 and 6.3 months, respectively. Best outcomes were observed in 4 patients who had a response to bridging therapy, suggesting that optimizing pre-CAR-T therapy may be key for improved outcomes. Our study suggests that CAR-T therapy in patients with CNS MM is safe and feasible, and screening for CNS involvement before CAR-T therapy could be warranted in high-risk patients. The excellent initial response but relatively short PFS suggests consideration for post-CAR-T maintenance. Larger studies are needed to confirm these findings.