Purpose of review: Lymphodepleting chemotherapy (LD) has emerged as a key determinant of chimeric antigen receptor T cell (CAR) efficacy across pediatric/adult B cell malignancies. Clinical trials demonstrate the superiority of fludarabine/cyclophosphamide (Flu/Cy) regimens, resulting in the adoption of Flu/Cy as the pre-CAR LD standard. In the context of a global fludarabine shortage, consideration of alternative regimens is timely, yet limited clinical data exists, specifically in the pediatric B-ALL CAR setting.
Recent findings: Bendamustine has been used as an effective LD prior to CD19-CAR in adult lymphoma. Although use in the pediatric CAR setting is limited, tolerability has been established in pediatric Hodgkin's lymphoma. Clofarabine is a purine nucleoside analog with mechanistic overlap with fludarabine; however, toxicity is high in the upfront leukemia setting, and thus use as an LD pre-CAR should be pursued with caution. We review the experience using bendamustine and clofarabine to serve as a resource when considering LD regimens as an alternative to fludarabine for pediatric B-ALL.
Keywords: Bendamustine; CAR T cells; Clofarabine; Fludarabine; Lymphodepletion; Pediatric B-acute lymphoblastic leukemia.
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.