1. Efficacy and safety of bendamustine for lymphodepletion before lisocabtagene maraleucel
- Author
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Guido Ghilardi, Luca Paruzzo, Vrutti Patel, Jakub Svoboda, Emeline R. Chong, Eugenio Fardella, Elise A. Chong, Giulia Gabrielli, Sunita D. Nasta, Daniel J. Landsburg, Jordan Carter, Raymone Pajarillo, Stefan K. Barta, Griffin White, Elizabeth Weber, Ellen Napier, David L. Porter, Alfred L. Garfall, Stephen J. Schuster, and Marco Ruella
- Subjects
Non-Hodgkin lymphoma (NHL) ,Chimeric antigen receptor T cells (CART) ,Lymphodepletion ,Bbendamustine ,Ccytokine-release syndrome (CRS) ,Immune effector cell associated neurotoxicity syndrome (ICANS) ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract 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.
- Published
- 2024
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