• Paula Rodriguez-Otero, Sikander Ailawadhi, Bertrand Arnulf, Krina Patel, Michele Cavo, Ajay K Nooka, Salomon Manier, Natalie Callander, Luciano J Costa, Ravi Vij, Nizar J Bahlis, Philippe Moreau, Scott R Solomon, Michel Delforge, Jesus Berdeja, Anna Truppel-Hartmann, Zhihong Yang, Linda Favre-Kontula, Fan Wu, Julia Piasecki, Mark Cook, and Sergio Giralt.
• From Clínica Universidad de Navarra, Pamplona, Spain (P.R.-O.); Mayo Clinic, Jacksonville, FL (S.A.); Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris (B.A.), Centre Hospitalier Universitaire de Lille, Université de Lille, Lille (S.M.), and University Hospital of Nantes, Nantes (P.M.) - all in France; M.D. Anderson Cancer Center, University of Texas, Houston (K.P.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and the Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University School of Medicine, Bologna, Italy (M. Cavo); Winship Cancer Institute of Emory University (A.K.N.) and Northside Hospital Cancer Institute (S.R.S.) - both in Atlanta; the University of Wisconsin Carbone Cancer Center, Madison (N.C.); the University of Alabama at Birmingham, Birmingham (L.J.C.); Washington University School of Medicine in St. Louis, St. Louis (R.V.); Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada (N.J.B.); Universitaire Ziekenhuizen Leuven, Leuven, Belgium (M.D.); Sarah Cannon Research Institute and Tennessee Oncology, Nashville (J.B.); 2seventy bio, Cambridge, MA (A.T.-H.); Bristol Myers Squibb, Princeton, NJ (Z.Y., L.F.-K., F.W., J.P., M. Cook); Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom (M. Cook); and Memorial Sloan Kettering Cancer Center, New York (S.G.).
• N. Engl. J. Med. 2023 Mar 16; 388 (11): 100210141002-1014.

BackgroundSurvival is poor among patients with triple-class-exposed relapsed and refractory multiple myeloma. Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, previously led to deep, durable responses in patients with heavily pretreated relapsed and refractory multiple myeloma.MethodsIn this international, open-label, phase 3 trial involving adults with relapsed and refractory multiple myeloma who had received two to four regimens previously (including immunomodulatory agents, proteasome inhibitors, and daratumumab) and who had disease refractory to the last regimen, we randomly assigned patients in a 2:1 ratio to receive either ide-cel (dose range, 150×106 to 450×106 CAR-positive T cells) or one of five standard regimens. The primary end point was progression-free survival. Key secondary end points were overall response (partial response or better) and overall survival. Safety was assessed.ResultsA total of 386 patients underwent randomization: 254 to ide-cel and 132 to a standard regimen. A total of 66% of the patients had triple-class-refractory disease, and 95% had daratumumab-refractory disease. At a median follow-up of 18.6 months, the median progression-free survival was 13.3 months in the ide-cel group, as compared with 4.4 months in the standard-regimen group (hazard ratio for disease progression or death, 0.49; 95% confidence interval, 0.38 to 0.65; P<0.001). A response occurred in 71% of the patients in the ide-cel group and in 42% of those in the standard-regimen group (P<0.001); a complete response occurred in 39% and 5%, respectively. Data on overall survival were immature. Adverse events of grade 3 or 4 occurred in 93% of the patients in the ide-cel group and in 75% of those in the standard-regimen group. Among the 225 patients who received ide-cel, cytokine release syndrome occurred in 88%, with 5% having an event of grade 3 or higher, and investigator-identified neurotoxic effects occurred in 15%, with 3% having an event of grade 3 or higher.ConclusionsIde-cel therapy significantly prolonged progression-free survival and improved response as compared with standard regimens in patients with triple-class-exposed relapsed and refractory multiple myeloma who had received two to four regimens previously. The toxicity of ide-cel was consistent with previous reports. (Funded by 2seventy bio and Celgene, a Bristol-Myers Squibb company; KarMMa-3 ClinicalTrials.gov number, NCT03651128.).Copyright © 2023 Massachusetts Medical Society.

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