更高剂量 tisagenlecleucel 与结局改善相关：来自儿科真实世界 CAR 联盟的报告

Remarkable complete response rates have been shown with tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting CD19, in patients up to age 26 years with refractory/relapsed B-cell acute lymphoblastic leukemia; it is US Food and Drug Administration approved for this indication.

Currently, patients receive a single dose of tisagenlecleucel across a wide dose range of 0. 2 to 5. 0 106 and 0. 1 to 2. 5 108 CAR T cells per kg for patients 50 and >50 kg, respectively. The effect of cell dose on survival and remission is not yet well established.

Our primary goal was to determine if CAR T-cell dose affects overall survival (OS), event-free survival (EFS), or relapse-free-survival (RFS) in tisagenlecleucel recipients. Retrospective data were collected from Pediatric Real World CAR Consortium member institutions and included 185 patients infused with commercial tisagenlecleucel. The median dose of viable transduced CAR T cells was 1. 7 106 CAR T cells per kg. To assess the impact of cell dose, we divided responders into dose quartiles: 0. 134 to 1. 300 106 (n = 48 [27%]), 1. 301 to 1.

700 106 (n = 46 [26%]), 1. 701 to 2. 400 106 (n = 43 [24%]), and 2. 401 to 5. 100 106 (n = 43 [24%]). OS, EFS, and RFS were improved in patients who received higher doses of tisagenlecleucel (P = . 031, . 0079, and . 0045, respectively). Higher doses of tisagenlecleucel were not associated with increased toxicity. Because the current tisagenlecleucel package insert dose range remains broad, this work has implications in regard to targeting higher cell doses, within the approved dose range, to optimize patients' potential for long-standing remission.