Safety and Efficacy of BCMA directed Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Plasma Cell Leukemia Open Access

• CAR-T is an effective and safe treatment option in patients with plasma cell leukemia.

• Despite similar objective responses with ide-cel and cilta-cel, patients with PCL derived greater benefit from cilta-cel rather than ide-cel

Despite significant therapeutic advances in multiple myeloma (MM), outcomes in patients with plasma cell leukemia (PCL) remain dismal. We conducted a multicenter retrospective analysis of patients with PCL treated with the B-cell Maturation Antigen (BCMA)-directed Chimeric Antigen Receptor T-Cell (CAR-T) products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). We identified 34 patients, 19 patients received ide-cel and 15 received cilta-cel. With a median follow-up of 11.9 months, the overall median progression free survival (mPFS) was 9.0 months (95% CI 4-15 months) and the median overall survival (mOS) was 13.0 months (95% CI 8-not estimable (NE) months). The 1-year cumulative incidence of progression or death was 72% and the 1-year cumulative incidence of death was 47%. Patients receiving cilta-cel had a longer mPFS (19.0 months vs 6.0 months) and mOS (>23 months (NE) vs 9.0 months) compared to those treated with ide-cel. Similarly, the 1-year cumulative incidence of disease progression or death was 37.5% (95% CI 17.4%-68.5%) with cilta-cel, while all patients treated with ide-cel progressed or died within 12 months of infusion. Rates of hematological and non-hematological toxicities were similar between those patients treated with cilta-cel and ide-cel and consistent with those reported in patients with MM. In this first multicenter study evaluating patients with PCL treated with standard of care CAR-T products, we show that CAR-T is safe, feasible, and associated with improved outcomes compared to historical standards.