CD19 CAR T-cell therapy and prophylactic anakinra in relapsed or refractory lymphoma: phase 2 trial interim results.

Autor: Park JH; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA. parkj6@mskcc.org.; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA. parkj6@mskcc.org.; Department of Medicine, Weill Cornell Medicine, New York City, NY, USA. parkj6@mskcc.org., Nath K; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Devlin SM; Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Sauter CS; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.; Center for Cell Engineering, Sloan Kettering Institute, New York City, NY, USA.; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA., Palomba ML; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.; Department of Medicine, Weill Cornell Medicine, New York City, NY, USA.; Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Shah G; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.; Department of Medicine, Weill Cornell Medicine, New York City, NY, USA.; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Dahi P; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.; Department of Medicine, Weill Cornell Medicine, New York City, NY, USA.; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Lin RJ; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.; Department of Medicine, Weill Cornell Medicine, New York City, NY, USA.; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Scordo M; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.; Department of Medicine, Weill Cornell Medicine, New York City, NY, USA.; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Perales MA; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.; Department of Medicine, Weill Cornell Medicine, New York City, NY, USA.; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Shouval R; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.; Department of Medicine, Weill Cornell Medicine, New York City, NY, USA.; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Tomas AA; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.; Division of Hematology and Hemotherapy, Hospital General Universitario Gregorio Maranon, Madrid, Spain., Cathcart E; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Mead E; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.; Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Santomasso B; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Holodny A; Radiology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Brentjens RJ; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.; Center for Cell Engineering, Sloan Kettering Institute, New York City, NY, USA.; Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Riviere I; Center for Cell Engineering, Sloan Kettering Institute, New York City, NY, USA.; Michael G. Harris Cell Therapy and Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Sadelain M; Center for Cell Engineering, Sloan Kettering Institute, New York City, NY, USA.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2023 Jul; Vol. 29 (7), pp. 1710-1717. Date of Electronic Publication: 2023 Jul 03.
DOI: 10.1038/s41591-023-02404-6
Abstrakt: In preclinical models, anakinra, an IL-1 receptor antagonist (IL-1Ra), reduced immune effector cell-associated neurotoxicity syndrome (ICANS) without compromising anti-CD19 chimeric antigen receptor (CAR) T-cell efficacy. We initiated a phase 2 clinical trial of anakinra in patients with relapsed/refractory large B-cell lymphoma and mantle cell lymphoma treated with commercial anti-CD19 CAR T-cell therapy. Here we report a non-prespecified interim analysis reporting the final results from cohort 1 in which patients received subcutaneous anakinra from day 2 until at least day 10 post-CAR T-cell infusion. The primary endpoint was the rate of severe (grade ≥3) ICANS. Key secondary endpoints included the rates of all-grade cytokine release syndrome (CRS) and ICANS and overall disease response. Among 31 treated patients, 74% received axicabtagene ciloleucel, 13% received brexucabtagene ciloleucel and 4% received tisagenlecleucel. All-grade ICANS occurred in 19%, and severe ICANS occurred in 9.7% of patients. There were no grade 4 or 5 ICANS events. All-grade CRS occurred in 74%, and severe CRS occurred in 6.4% of patients. The overall disease response rate was 77% with 65% complete response rate. These initial results show that prophylactic anakinra resulted in a low incidence of ICANS in patients with lymphoma receiving anti-CD19 CAR T-cell therapy and support further study of anakinra in immune-related neurotoxicity syndromes.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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