CD19 CAR T cell therapy is an effective strategy for first CNS relapse in pediatric b ALL

作者：Amanda M. DiNofia, Regina M. Myers, Yimei Li, Hongyan Liu, Richard Aplenc, Diane Baniewicz, Allison Barz Leahy, Lucy E. Cain, Colleen Callahan, Caroline Diorio, Joseph A. Fraietta, Elizabeth O. Hexner, Caitlin Hopkins, Stephen P. Hunger, Vanessa Gonzalez, Julie K. Jadlowsky, Mariam Kerolos, Raabia Khan, Susan McClory, Shannon L. Maude, Gabriela Plesa, Susan R. Rheingold, Mackenzie Stewart, Sarah K. Tasian, Melissa Varghese, Lisa Wray, Stephan A. Grupp · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-648 · 被引用次数：4 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research、Biomedical Ethics and Regulation

Abstract Introduction: The 4-year disease-free survival (DFS) of children with first isolated central nervous system (iCNS) relapse treated on the most recent Children's Oncology Group AALL1331 randomized phase 3 trial was extremely poor at 24%, and the addition of blinatumomab failed to improve outcomes. Cranial radiation (cXRT) is the standard of care (SOC) for CNS relapse but can have profound neurologic consequences. More effective and less toxic strategies are urgently needed. We hypothesized that CD19-targeted CAR T cell therapy (CART19) could lead to durable remissions in patients with CNS-relapsed B-ALL and obviate the need for cXRT or hematopoietic cell transplant (HCT). We conducted a Phase 2 trial of CTL019, the construct that was FDA approved as tisagenlecleucel, for this population (NCT04276870). Methods: Patients 0-29 years (y) of age with CNS relapse of B-ALL without receipt of cXRT for this relapse were lymphodepleted with fludarabine/cyclophosphamide prior to infusion with 5x106 CART19 cells/kg. Results: From March 2020 to April 2025, 43 patients were enrolled and infused with CART19; 39 (91%) had first CNS relapse (3 second, 1 third). Thirty-six patients (84%) had iCNS relapse. Median age at infusion was 8y (range 1-26y); 44% were female. Six (14%) patients were Hispanic; of those not Hispanic, 72% were White, 11% other, 8% Black, 6% unknown, 3% Asian. Only the 4 patients in ≥2nd relapse had received prior cXRT and/or total body irradiation (TBI). Ten (23%) ...