Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Stephen J. SchusterFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellMichael BishopFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellConstantine S. TamFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellEdmund K. WallerFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellPeter BorchmannFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellJoseph P. McGuirkFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellUlrich JägerFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellSamantha JaglowskiFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellCharalambos AndreadisFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellJason R. WestinFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellIsabelle FleuryMaisonneuve-Rosemont Hospital, University of Montreal, MontrealVeronika BachanováFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellS.R. FoleyFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellP. Joy HoFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellStephan MielkeFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellJohn MagenauFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellHarald HolteFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellSerafino PantanoFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellLida PacaudFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellRakesh AwasthiFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellJufen ChuFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellÖzlem AnakFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellGilles SallesFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem CellRichard T. MaziarzFrom the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (S.J.S.); the Hematopoietic Cellular Therapy Program, University of Chicago Medicine, Chicago (M.R.B.); Peter MacCallum Cancer Centre, St. Vincent’s Hospital and University of Melbourne, Melbourne, VIC (C.S.T.), and the Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Sydney (P.J.H.) — both in Australia; Winship Cancer Institute of Emory University, Bone Marrow and Stem Cell
2018en
ABI
Аннотация
BACKGROUND: Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. METHODS: We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. The primary end point was the best overall response rate (i.e., the percentage of patients who had a complete or partial response), as judged by an independent review committee. RESULTS: A total of 93 patients received an infusion and were included in the evaluation of efficacy. The median time from infusion to data cutoff was 14 months (range, 0.1 to 26). The best overall response rate was 52% (95% confidence interval, 41 to 62); 40% of the patients had complete responses, and 12% had partial responses. Response rates were consistent across prognostic subgroups. At 12 months after the initial response, the rate of relapse-free survival was estimated to be 65% (79% among patients with a complete response). The most common grade 3 or 4 adverse events of special interest included cytokine release syndrome (22%), neurologic events (12%), cytopenias lasting more than 28 days (32%), infections (20%), and febrile neutropenia (14%). Three patients died from disease progression within 30 days after infusion. No deaths were attributed to tisagenlecleucel, cytokine release syndrome, or cerebral edema. No differences between response groups in tumor expression of CD19 or immune checkpoint-related proteins were found. CONCLUSIONS: In this international study of CAR T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma in adults, high rates of durable responses were produced with the use of tisagenlecleucel. (Funded by Novartis; JULIET ClinicalTrials.gov number, NCT02445248 .).
Перевод пока недоступен
Идентификаторы
Цитирования и источники
Цитирований: 3Использованных источников: 0