Bendamustine Is Less Toxic Than Fludarabine-Cyclophosphamide-Based Lymphodepletion before CD28-Costimulated CART19 through Reduced Inflammatory Cytokines

Introduction: Lymphodepletion (LD) is an integral component of anti-CD19 chimeric antigen receptor T cell (CART19) immunotherapy, creating the proper environment and cytokine milieu for CART engraftment and function. We previously demonstrated that bendamustine (Benda) LD is as effective as standard fludarabine and cyclophosphamide (Flu/Cy) LD prior to 4-1BB-costimulated tisagenlecleucel but is characterized by significantly reduced cytokine-release syndrome (CRS), neurotoxicity (ICANS), and hematological toxicities. However, whether Benda LD is also effective and safe in CD28 costimulated CART19, and the mechanism for the reduced toxicities associated with Benda LD remain unknown.