Incidence of Parkinsonism As a Complication of Anti-BCMA CAR-T Cell Therapy in Multiple Myeloma

Abstract

Introduction: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR T) therapy has revolutionized the treatment for relapsed/refractory multiple myeloma (RRMM). Two BCMA-directed CAR T products, Idecabtagene Vicleucel (ide-cel) and Ciltacabtagene Autoleucel (cilta-cel), have received approval from the U.S. Food and Drug Administration (FDA). While these therapies have demonstrated remarkable efficacy, concerns regarding treatment-related neurotoxicities have emerged. The specific adverse effect of Parkinsonism associated with BCMA-directed CAR T therapy has not been adequately studied. Methods: We conducted an analysis utilizing the FDA Adverse Events Reports System (FAERS) database, covering the years 2021-2023. Our search focused on the reported incidence of Parkinsonism associated with BCMA-directed CAR T therapy. Results: Upon reviewing the FDA data, we identified a total of 177 patients with reported nervous system disorders related to Ide-cel therapy. Out of these patients, 2 had reported incidents of Parkinsonism. Similarly, for Cilta-cel therapy, there were 81 patients with reported nervous system disorders, with 5 reported incidents of Parkinsonism. Out of the total 7 reported patients with Parkinsonism, 5 were males, 2 were females, the average age was 67, the average weight was 68.9 kg, and 3 patients were also noted to have associated cytokine release syndrome. Conclusion: Our analysis of FAERS data highlights the occurrence of Parkinsonism associated with BCMA-directed CAR T-cell therapy. Further studies are required to quantify the need for neurological surveillance after initiating treatment with these novel agents.