TY - JOUR
T1 - Has the shortage of fludarabine altered the current paradigm of lymphodepletion in favor of bendamustine?
AU - Filioglou, Dimitrios
AU - Husnain, Muhammad
AU - Khurana, Sharad
AU - Simpson, Richard J.
AU - Katsanis, Emmanuel
N1 - Publisher Copyright:
Copyright © 2023 Filioglou, Husnain, Khurana, Simpson and Katsanis.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - bendamustine
KW - CAR (chimeric antigen receptor) T cells
KW - cyclophosphamide
KW - fludarabine
KW - lymphodepletion
UR - http://www.scopus.com/inward/record.url?scp=85178942375&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85178942375&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2023.1329850
DO - 10.3389/fimmu.2023.1329850
M3 - Article
C2 - 38077398
AN - SCOPUS:85178942375
SN - 1664-3224
VL - 14
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1329850
ER -