BCMA-directed CAR-T treatment for Refractory Multiple Myeloma

Introduction: CAR-T cell therapies targeting B-cell maturation antigen (BCMA) show significant promise for relapsed/refractory multiple myeloma (RRMM). However, lengthy manufacturing times and variable T-cell quality cause critical treatment delays. This retrospective study analyzed outcomes and attrition reasons for patients who never receive their infusion after completing T-cell collection, evaluating survival outcomes from the date of apheresis to capture this manufacturing window.

Methods: This retrospective study at Hackensack University Medical Center evaluated RRMM patients who underwent T-cell apheresis for BCMA-targeted CAR-T therapies (idecabtagene vicleucel or ciltacabtagene autoleucel) between January 1, 2021, and April 30, 2024. Progression-free survival (PFS) and overall survival (OS) were calculated from the baseline date of cell collection. Survival curves were analyzed using the Kaplan-Meier method and compared via log-rank tests.

Results: Of 99 patients who underwent apheresis, 12% (n=12) never received the final CAR-T product. No significant differences in median age, high-risk cytogenetics, or prior lines of therapy (median: 5) were found between the infused (n=87) and non-infused (n=12) groups. While specific descriptive data on bridging therapy regimens were unavailable for this cohort, disease progression (100% vs. 39.08%, p<0.005) and mortality (83.3% vs. 19.54%, p<0.005) were significantly higher in the non-infused group, with 58% missing infusion due to progression or death. From apheresis, median PFS was 17.5 months for the infused group versus 1.5 months for the non-infused group (p<0.0001). Median OS was not reached in the infused group but was 1.9 months for the non-infused group (p<0.0001).

Conclusion: The period between apheresis and infusion is a high-risk window where 12% of patients experience rapid clinical decline or death. This highlights a potential need to explore optimized bridging protocols and expedited manufacturing. Future clinical trials should calculate survival baselines from the date of apheresis to accurately capture the true clinical journey.