Pre-leukapheresis Risk Factors for BCMA CAR-T cell Product Manufacturing Failure

B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapies have transformed treatment for relapsed/refractory (R/R) multiple myeloma (MM). Manufacturing failures are a barrier to therapy delivery. Understanding modifiable risk factors of manufacturing failures could improve patient selection and leukapheresis timing. We conducted a multi-center retrospective case-control study of patients with MM who underwent leukapheresis for idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel) manufacturing between 2021 to 2024. We analyzed the relationship between prior therapy exposure and manufacturing outcomes with a focus on length of time since last exposure by drug class. Among the 43 patients (30 ide-cel, 13 cilta-cel), 8 patients (18.6%) experienced manufacturing failures. Exposure to alkylating agents was associated with lower odds of manufacturing success. Every additional month from last exposure to alkylating agents resulted in a 7% reduction in odds of manufacturing failure (OR 0.93, 95% CI 0.87-0.98, p<0.01). No significant associations were identified between manufacturing failure and time since exposure to proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies, or selinexor. Differences in patient/disease characteristics were not associated with manufacturing failure. Optimizing timing of leukapheresis relative to alkylating agent exposure may reduce manufacturing failure rates. Larger multicenter studies are needed to validate these findings and assess the impact of new agents.