Simulation studies of age-adjusted FLU dosage regimens to improve outcomes in CAR T-cell therapy
Panetta JC, Talleur AC, Naik S, et al. Age-Adjusted Dosing of Fludarabine for Lymphodepletion in CAR T-Cell Therapy: A Clinical Trial Simulation Study. Blood Advances. 2025; (doi: 10.1182/bloodadvances.2025015928).
Fludarabine is valued for its role in chimeric antigen receptor (CAR) T-cell therapy, but scientists believe moving away from fixed dosages could mediate better outcomes. Among children with acute lymphoblastic leukemia, the likelihood of relapse goes down and the chance of leukemia-free survival goes up the greater their systemic exposure to fludarabine. The effects of the lymphodepletion agent, which improves CAR T-cell persistence and expansion in vivo, are most pronounced in younger children. To identify age-adjusted dosage strategies that might support effective fludarabine exposure, investigators employed modeling scenarios and clinical trial simulations. The research determined that 22%-61% of patients on fixed-dose fludarabine fell within the target range, defined as cumulative area under the curve of 13.8 to 25 mgxhr/L. The estimate climbed to 72% with age-adjusted dosing and to 94% for dosages based on therapeutic drug monitoring. The research also suggested these alternate dosing strategies (age-based or therapeutic drug monitoring) could potentially curtail the number of relapsing patients by 72% within 1 year and increase overall survival to 67% by 2 years.