Comparison of Fludarabine/Cyclophosphamide Vs Bendamustine As Lymphodepleting Regimen for CAR-T: A Safety and Efficacy Analysis in Patients with Relapsed/ Refractory Multiple Myeloma

Background Two commercially available anti-BCMA chimeric antigen receptor T-cell therapies (CAR-T) are approved by FDA for use in patients with relapsed multiple myeloma (RRMM). Lymphodepletion (LD) with fludarabine in combination with cyclophosphamide (Flu/Cy) is used as a standard regimen sequentially prior to CAR-T. Due to a national shortage with regards to availability of fludarabine, bendamustine (B) has emerged as a possible alternative regimen for LD. We evaluated the impact of bendamustine as an alternative lymphodepleting regimen to Flu/Cy on safety and efficacy profile of CAR-T therapy in patients with relapsed multiple myeloma. Patients and methods We conducted a single center, retrospective, IRB-approved study for patients with RRMM who received LD with B and FC at Hackensack University Medical Center (HUMC). Efficacy outcomes included overall response rates (ORR), Progression free survival (PFS) and Overall survival (OS). Response to CAR-T was assessed by the treating physician per International Myeloma Working Group (IMWG) criteria. Safety outcomes included the incidence and severity of adverse events (AEs). AEs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE 5.0). Cytokine release syndrome (CRS) and immune effector associated neurotoxicity syndrome (ICANS) were graded as per the American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Results We identified 53 patients with RRMM who received anti-BCMA CAR-T therapy between 6/2021 and 6/2023, who had a follow-up of at least 30 days following infusion. Due to shortage of fludarabine, the majority of pts (67.9%) received LD with B. Baseline characteristics are described in table 1. The median age of the entire cohort was 69.6 years, not significantly different between the B vs FC group. There were no statistically significant differences between the two groups with respect to the baseline characteristics except more pts were male in the B group (66.7% vs 32.1%, p=0.03) and the type of CAR-T product received. No significant differences were found with regards to the safety profile; however, the ORR were found to be higher in the FC group compared to the B group (88.2% vs 69.4%) although not statistically significant (p=0.1). Median PFS (mPFS) was shorted in the B group compared with the FC group (7.7 months vs 13.1 months) respectively (p=0.0047). Median OS (mOS) was not reached in the FC group, whereas it was 1