Reinfusion of CD19 CAR T cells for relapse prevention and treatment in children with acute lymphoblastic leukemia

作者：Regina M. Myers, Kaitlin J. Devine, Yimei Li, Sophie Lawrence, Allison Barz Leahy, Hongyan Liu, Lauren M. Vernau, Colleen A. Callahan, Diane Baniewicz, Stephan Kadauke, Regina McGuire, Gerald B. W. Wertheim, Irina M. Kulikovskaya, Vanessa E. Gonzalez, Joseph A. Fraietta, Amanda M. DiNofia, Stephen P. Hunger, Susan R. Rheingold, Richard Aplenc, Carl H. June, Stephan A. Grupp, Lisa Wray, Shannon L. Maude · 发表于：Blood Advances · 年份：2024 · DOI：10.1182/bloodadvances.2024012885 · 被引用次数：32 · 研究领域：CAR-T cell therapy research、Advancements in Semiconductor Devices and Circuit Design、Integrated Circuits and Semiconductor Failure Analysis

ABSTRACT: Relapse after CD19-directed chimeric antigen receptor (CAR)-modified T cells remains a substantial challenge. Short CAR T-cell persistence contributes to relapse risk, necessitating novel approaches to prolong durability. CAR T-cell reinfusion (CARTr) represents a potential strategy to reduce the risk of or treat relapsed disease after initial CAR T-cell infusion (CARTi). We conducted a retrospective review of reinfusion of murine (CTL019) or humanized (huCART19) anti-CD19/4-1BB CAR T cells across 3 clinical trials or commercial tisagenlecleucel for relapse prevention (peripheral B-cell recovery [BCR] or marrow hematogones ≤6 months after CARTi), minimal residual disease (MRD) or relapse, or nonresponse to CARTi. The primary endpoint was complete response (CR) at day 28 after CARTr, defined as complete remission with B-cell aplasia. Of 262 primary treatments, 81 were followed by ≥1 reinfusion (investigational CTL019, n = 44; huCART19, n = 26; tisagenlecleucel, n = 11), representing 79 patients. Of 63 reinfusions for relapse prevention, 52% achieved CR (BCR, 15/40 [38%]; hematogones, 18/23 [78%]). Lymphodepletion was associated with response to CARTr for BCR (odds ratio [OR], 33.57; P = .015) but not hematogones (OR, 0.30; P = .291). The cumulative incidence of relapse was 29% at 24 months for CR vs 61% for nonresponse to CARTr (P = .259). For MRD/relapse, CR rate to CARTr was 50% (5/10), but 0/8 for nonresponse to CARTi. Toxicity was generally mild, with the only gr...