Comparison of Fludarabine Versus Bendamustine as a Lymphodepleting Chemotherapy Prior to CAR-T for Large Cell...

Lymphodepleting chemotherapy (LD) enhances chimeric antigen receptor T cell (CAR-T) expansion, persistence, and clinical activity. Fludarabine-cyclophosphamide is most used, but the benefit of alternative agents is unknown. This study compares fludarabine- versus bendamustine-based LD in the real-world setting prior to CAR-T treatment of relapsed or refractory large cell lymphoma (LBCL). We assessed outcomes of patients with LBCL who received commercial CD19 CAR-T therapies during 2017 to 2023, using data from Center for International Blood and Marrow Transplant Research. Of 5256 patients with LBCL treated with axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel, 92% and 9% received fludarabine and bendamustine LD, respectively. Multivariate analyses showed bendamustine had inferior overall response rate (ORR) (hazard ratio [HR] 0.773, P = .0013), but there was no difference in complete response (HR 0.828, P = .0606). The 1-year and 2-year rates of progression-free survival (PFS) were lower for bendamustine (P = .04), and the 1-year and 2-year rates of overall survival (OS) were similar (P = .65) The bendamustine group had lower rates of toxicities than the fludarabine group, including severe cytokine release syndrome (odds ratio [OR] 0.445, P < .0001), immune effector cell-associated neurotoxicity syndrome (OR 0.432, P < .0001), prolonged cytopenia (OR 0.479, P < .0001) Treatment-related mortality (TRM) was lower in the bendamustine group. In a subset analysis adjusting for distribution of LD regimens, the main conclusions were the same. Regardless of CAR-T products used, compared to patients who received bendamustine, patients who received fludarabine LD had higher ORR and PFS, without significant impact on OS. Bendamustine was associated with a reduced incidence of toxicities and TRM. Providers can consider relevant patient characteristics when choosing LD and the trade-off between efficacy and safety. Bendamustine can be considered an alternative LD prior to CAR-T for LBCL.