氟达拉滨与苯达莫司汀作为大细胞淋巴瘤 CAR-T 前淋巴细胞清除化疗的比较

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.