BCMA-directed CAR T-cell Therapy in patients with multiple myeloma and CNS involvement

We investigated BCMA-directed CART in patients with relapsed or refractory multiple myeloma (RRMM) and CNS involvement. Ten patients who received either ide-cel (n=6) or cilta-cel (n=4) were included in this analysis. Patients had brain/cranial nerve and/or spinal cord involvement/leptomeningeal disease evident on either MRI (100%) and/or CSF (40%). The time between CNS diagnosis and CART was 60 days or less in 50% of patients, >300 days in 30%, and 20% were diagnosed within 14 days after CART infusion. Seven (70%) received CNS-directed therapy during bridging in the form of different combinations of radiotherapy, intrathecal chemotherapy, and surgery. There were no excess toxicities: no CRS grade (G) 3 or more, ICANS G3 10% (n=1), and none had ICANS G4. Two patients experienced delayed but treatable neurotoxicity with no reported Parkinsonian side effects. The best overall response rate was 80%, with 70% VGPR or better, and a 100% CNS response. For patients with CNS myeloma diagnosed pre-CART (n=8), with a median follow-up of 381 days, the median OS and PFS were 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-CART therapy may be key for improved outcomes. Our study suggests that CART in patients with CNS MM is safe and feasible and that screening for CNS involvement before CART therapy could be warranted in high-risk patients. The excellent initial response but relatively short PFS suggests consideration for post-CART maintenance. Larger studies are needed to confirm these findings.