Higher doses of tisagenlecleucel associate with improved outcomes: a report from the pediatric real-world CAR consortium.

Tisagenlecleucel, chimeric antigen receptor T cell (CART) therapy targeting CD19, has shown remarkable complete response (CR) rates for patients up to the age of 26 with refractory/relapsed B-cell acute lymphoblastic leukemia (B-ALL), and is FDA-approved for this indication. Currently, patients receive a single dose of tisagenlecleucel across a wide dose range of 0.2- 5.0 x 106 CAR T cells/kg for patients ≤ 50 kg, or 0.1- 2.5 x 108 CAR T cells for patients > 50 kg. The effect of cell dose on survival and remission has yet to be well-established. Our primary goal was to determine if CART cell dose impacts overall survival (OS), event-free survival (EFS) and relapse-free-survival (RFS) in tisagenlecleucel-recipients. Retrospective data were collected from the Pediatric Real World CAR Consortium (PRWCC) member institutions and included 185 patients infused with commercial tisagenlecleucel. The median dose of viable transduced CAR T cells was 1.7 x106 CAR T cells/kg. To assess the impact of cell dose, we divided the responders into dose quartiles: 0.134-1.300 x 106 (D1; n=48 (27%), 1.301-1.700 x 106 (D2; n=46 (26%), 1.701-2.400 x 106(D3; n=43 (24%) and 2.401-5.100 x 106 (D4; n=43 (24%). OS, EFS, and RFS were improved in patients that received higher doses of Tisagenlecleucel (p=0.031, 0.0079 and 0.0045 respectively). Moreover, higher doses of tisagenlecleucel were not associated with increased toxicity. As the current tisagenlecleucel package insert dose-range remains broad, this work has implications in regard to targeting higher cell doses to optimize patients for long-standing remission.