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Has the shortage of fludarabine altered the current paradigm of lymphodepletion in favor of bendamustine?
Filioglou, Dimitrios; Husnain, Muhammad; Khurana, Sharad; Simpson, Richard J; Katsanis, Emmanuel.
Affiliation
  • Filioglou D; Department of Pediatrics, University of Arizona, Tucson, AZ, United States.
  • Husnain M; Department of Medicine, University of Arizona, Tucson, AZ, United States.
  • Khurana S; The University of Arizona Cancer Center, Tucson, AZ, United States.
  • Simpson RJ; Department of Medicine, University of Arizona, Tucson, AZ, United States.
  • Katsanis E; The University of Arizona Cancer Center, Tucson, AZ, United States.
Front Immunol ; 14: 1329850, 2023.
Article in En | MEDLINE | ID: mdl-38077398
The most common lymphodepletion regimen used prior to infusion of chimeric antigen receptor-T cells (CAR-T) is cyclophosphamide (CY) in combination with fludarabine (Flu) (CY-FLU). While cyclophosphamide (CY) possesses lymphotoxic effects, it concurrently preserves regulatory T cell activity, potentially affecting the efficacy of CAR-T cells. Moreover, the use of fludarabine (FLU) has been linked to neurotoxicity, which could complicate the early detection of immune effector cell-associated neurotoxicity syndrome (ICANS) observed in CAR-T cell therapy. Given the ongoing shortage of FLU, alternative lymphodepleting agents have become necessary. To date, only a limited number of studies have directly compared different lymphodepleting regimens, and most of these comparisons have been retrospective in nature. Herein, we review the current literature on lymphodepletion preceding CAR-T cell therapies for lymphoid hematologic malignancies, with a specific focus on the use of bendamustine (BEN). Recent evidence suggests that administering BEN before CAR-T cell infusion yields comparable efficacy, possibly with a more favorable toxicity profile when compared to CY-FLU. This warrants further investigation through randomized prospective studies.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / Receptors, Chimeric Antigen Language: En Journal: Front Immunol Year: 2023 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / Receptors, Chimeric Antigen Language: En Journal: Front Immunol Year: 2023 Document type: Article Affiliation country: Country of publication: