Has the shortage of fludarabine altered the current paradigm of lymphodepletion in favor of bendamustine?

Dimitrios Filioglou, Muhammad Husnain, Sharad Khurana, Richard J. Simpson, Emmanuel Katsanis

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number1329850
JournalFrontiers in immunology
StatePublished - 2023


  • bendamustine
  • CAR (chimeric antigen receptor) T cells
  • cyclophosphamide
  • fludarabine
  • lymphodepletion

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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