• Stephen J Schuster, Michael R Bishop, Constantine S Tam, Edmund K Waller, Peter Borchmann, Joseph P McGuirk, Ulrich Jäger, Samantha Jaglowski, Charalambos Andreadis, Jason R Westin, Isabelle Fleury, Veronika Bachanova, S Ronan Foley, P Joy Ho, Stephan Mielke, John M Magenau, Harald Holte, Serafino Pantano, Lida B Pacaud, Rakesh Awasthi, Jufen Chu, Özlem Anak, Gilles Salles, Richard T Maziarz, and JULIET Investigators.
• From 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 Transplant Center, Atlanta (E.K.W.); the Department of Hematology and Oncology, University Hospital of Cologne, Cologne (P.B.), and the Würzburg University Medical Center, Center for Allogeneic Stem Cell Transplantation, Würzburg (S.M.) - both in Germany; the Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Cancer Center, Kansas City (J.P.M.); the Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna (U.J.); James Cancer Hospital and Solove Research Institute, Ohio State University Comprehensive Cancer Center, Columbus (S.J.); the Department of Hematology and Blood and Marrow Transplant, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (C.A.); the Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston (J.R.W.); Maisonneuve-Rosemont Hospital, University of Montreal, Montreal (I.F.), and the Juravinski Hospital and Cancer Centre, McMaster University, Hamilton, ON (S.R.F.) - both in Canada; the Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis (V.B.); Karolinska Institutet and University Hospital, Department of Laboratory Medicine/Department of Cell Therapy and Allogeneic Stem Cell Transplantation, Stockholm (S.M.); University of Michigan Comprehensive Cancer Center, Ann Arbor (J.M.M.); the Department of Oncology, Oslo University Hospital, Oslo (H.H.); Novartis Pharma, Basel, Switzerland (S.P., O.A.); Novartis Pharmaceuticals (L.B.P., J.C.) and Novartis Institutes for BioMedical Research (R.A.), East Hanover, NJ; the Department of Hematology, Hospices Civils de Lyon, Université de Lyon, Lyon, France (G.S.); and the Center for Hematologic Malignancies, Oregon Health and Science University Knight Cancer Institute, Portland (R.T.M.).
• N. Engl. J. Med. 2019 Jan 3; 380 (1): 45-56.

BackgroundPatients 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.MethodsWe 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.ResultsA 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.ConclusionsIn 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 .).

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