Comparison of Bendamustine and Flu/Cy Lymphodepletion Before BCMA CAR-T Therapy in MM

Overview

This study compared bendamustine versus fludarabine/cyclophosphamide (Flu/Cy) lymphodepletion in 56 multiple myeloma patients receiving BCMA CAR-T therapy. Both regimens achieved effective lymphodepletion with comparable CAR-T expansion, safety profiles, and clinical responses, suggesting bendamustine as a viable alternative during fludarabine shortages.

Background

BCMA-directed CAR-T therapies, idecabtagene vicleucel and ciltacabtagene autoleucel, are approved for relapsed multiple myeloma. Lymphodepletion prior to CAR-T infusion enhances CAR-T expansion and efficacy, with Flu/Cy being the standard regimen. Due to a global fludarabine shortage in 2022, bendamustine was adopted as an alternative lymphodepletion agent. This study evaluates the safety, efficacy, and hematologic effects of bendamustine compared to Flu/Cy in standard-of-care BCMA CAR-T therapy.

Data Highlights

Key Findings

• No significant differences in baseline patient characteristics between bendamustine and Flu/Cy groups.
• Bendamustine achieved effective lymphodepletion with higher median ALC on infusion day compared to Flu/Cy.
• Neutrophil counts varied over time, with Flu/Cy showing lower ANC early post-infusion but higher ANC at day 30 compared to bendamustine.
• CAR-T cell expansion measured by flow cytometry was comparable between both lymphodepletion regimens.
• Safety profiles including cytokine release syndrome and neurotoxicity were similar across groups.
• Clinical response rates and survival outcomes did not differ significantly between bendamustine and Flu/Cy cohorts.

Clinical Implications

Bendamustine is a feasible alternative lymphodepletion regimen for BCMA CAR-T therapy in multiple myeloma, especially during fludarabine shortages. It provides effective lymphodepletion without compromising CAR-T expansion or clinical outcomes. Clinicians may consider bendamustine to maintain treatment continuity when Flu/Cy is unavailable.

Conclusion

Bendamustine lymphodepletion demonstrates comparable safety, efficacy, and CAR-T expansion to standard Flu/Cy in BCMA CAR-T therapy for multiple myeloma, supporting its use as an alternative regimen during fludarabine shortages.

References

1. Idecabtagene vicleucel and ciltacabtagene autoleucel approvals [1,2,3]
2. Lymphodepletion improves CAR-T efficacy [4,5,6,7]
3. Initial cilta-cel study with cyclophosphamide alone [8]
4. Fludarabine shortage in 2022 [9]
5. ASTCT criteria for CRS and ICANS [10,11]
6. IMWG response criteria [12]
7. Bendamustine lymphodepletion in CD19 CAR-T [13,14]