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

Autor:	Myers RM; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Devine K; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Li Y; Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Lawrence S; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA., Leahy AB; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Liu H; Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA., Vernau L; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA., Callahan C; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA., Baniewicz D; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA., Kadauke S; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., McGuire R; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA., Wertheim GB; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Kulikovskaya I; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Gonzalez VE; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Fraietta JA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., DiNofia AM; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Hunger SP; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Rheingold SR; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Aplenc R; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., June CH; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Grupp SA; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Wray L; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Maude SL; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 May 14; Vol. 8 (9), pp. 2182-2192.
DOI:	10.1182/bloodadvances.2024012885
Abstrakt:	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 grade ≥3 cytokine release syndrome (n = 6) or neurotoxicity (n = 1) observed in MRD/relapse treatment. Reinfusion of CTL019/tisagenlecleucel or huCART19 is safe, may reduce relapse risk in a subset of patients, and can reinduce remission in CD19+ relapse. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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