CELL INTELLIGENCE · 肿瘤细胞治疗研究

Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. However, bendamustine as lymphodepletion prior to lisocabtagene maraleucel (liso-cel), a 4-1BB co-stimulated, fixed CD4:CD8 ratio anti-CD19 CART product, has not been described yet. Thus, we studied a cohort of sequentially-treated patients with large B-cell lymphomas who received bendamustine lymphodepletion before liso-cel at the University of Pennsylvania between 5/2021 and 12/2023 (n = 31). Patients were evaluated for toxicities and responses. Of note, 7 patients (22.6%) would have dnot met the inclusion criteria for the registrational liso-cel clinical trials, mostly due to older age. Overall and complete response rates were 76.9% and 73.1%, respectively. At a median follow-up of 6.3 months, the 6-month progression-free and overall survival were 59.9% and 91.1%, respectively. Rates of cytokine-release syndrome (CRS) and neurotoxicity (ICANS) of any grade were 9.7% and 9.7%, respectively, with no grade ≥ 3 events. No infections were reported during the first 30 days following liso-cel infusion. Neutropenia ≥ grade 3 was observed in 29.0% of patients; thrombocytopenia ≥ grade 3 occurred in 9.7%. In conclusion, bendamustine lymphodepletion before liso-cel appears to be a strategy that can drive tumor responses while ensuring a mild toxicity profile.