Age-adjusted dosing of fludarabine for lymphodepletion in CAR T-cell therapy: a clinical trial simulation study.

ABSTRACT:

Abstract

Fludarabine (FLU) is used for lymphodepletion and improves the persistence and expansion of chimeric antigen receptor (CAR) T cells in vivo. Higher FLU systemic exposure is associated with lower relapse risk and improved leukemia-free survival in pediatric patients with acute lymphoblastic leukemia treated with CD19 CAR T-cell therapy. FLU pharmacokinetics (PKs) is age dependent, with increased clearance in younger children. Here, we used modeling and simulation, including clinical trial simulations, to define age-adjusted FLU dosage regimens that may maintain effective FLU exposures and improve outcomes. The FLU PK and pharmacodynamic relationships with overall survival (OS) and cumulative incidence of relapse (CIR) were derived from published pediatric populations. Four

SUBMITTER: Panetta JC 

PROVIDER: S-EPMC12496251 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature