Dekker L, Calkoen FGJ, Jiang Y, et al. Fludarabine Exposure Predicts Outcome After CD19 CAR T-Cell Therapy in Children and Young Adults with Acute Leukemia. Blood Advances. 2022; (doi: 10.1182/bloodadvances.2021006700).
Leukemia-free survival in children and young adults with relapsed/refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL) improved following CD19 chimeric antigen receptor (CAR) T-cell infusion when cumulative fludarabine AUCT0-8 ≥14 mg*h/L. The retrospective study evaluated the effect of cumulative fludarabine exposure during lymphodepletion defined as concentration-time curve (AUC) on clinical outcome and lymphocyte kinetics. The analysis included 26 patients who received tisagenlecleucel for r/r B-ALL. Exposure of fludarabine was found to be predictive of leukemia-free survival, B cell aplasia, and CD19-positive relapse following CAR T-cell infusion. A cumulative fludarabine AUCT0-8 ≥14 mg*h/L yielded minimal event probability, while an AUCT0-8 <14 mg*h/L was classified as underexposure. The median leukemia-free survival was 1.8 months in the underexposed cohort, while the incidence of CD19-positive relapse within 1 year was 100%. This topped the relapse occurrence in the AUCT0-8 ≥14 mg*h/L group. The underexposed cohort also had a shorter B cell aplasia duration within 6 months. Optimizing fludarabine exposure may result in improved clinical outcome following CD19 CAR-T therapy.