ArticleTransplantation and cellular therapy2026
Comparison of Fludarabine Versus Bendamustine as a Lymphodepleting Chemotherapy Prior to CAR-T for Large Cell Lymphoma.
Article in Transplantation and cellular therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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