Optimizing fludarabine exposure during lymphodepletion to improve the efficacy of CAR-T cell therapy in children and young adults with B-ALL

Chimeric antigen receptor (CAR) T cell therapy is potentially curative for patients with relapsed or refractory acute lymphoblastic leukemia. However, long-term remission only occurs in 40-50% of responding patients, demonstrating a need to improve this therapy. The lymphodepleting regimen with fludarabine and cyclophosphamide has been demonstrated to improve clinical outcome by increasing expansion and persistence of CAR T cells. In this randomized, multicenter study in children and young adults with B-ALL, we aim to improve event free survival by optimizing fludarabine exposure prior to CAR T cell therapy using therapeutic drug monitoring. Through targeted fludarabine exposure as part of lymphodepletion there is a potential to enhance anti-leukemia response and improve long-term outcomes.

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Jobke Plaisier