• Jesús San-Miguel, Binod Dhakal, Kwee Yong, Andrew Spencer, Sébastien Anguille, María-Victoria Mateos, Fernández de LarreaCarlosCFrom the Cancer Center Clínica Universidad de Navarra, Centro Investigación Medica Aplicada, Instituto de Investigación de Navarra, Centro Investigación Biomédica en Red Cáncer (CIBERONC), Pamplona (J.S.-M.), the University Hospi, Joaquín Martínez-López, Philippe Moreau, Cyrille Touzeau, Xavier Leleu, Irit Avivi, Michele Cavo, Tadao Ishida, Seok Jin Kim, Wilfried Roeloffzen, van de DonkNiels W C JNWCJFrom the Cancer Center Clínica Universidad de Navarra, Centro Investigación Medica Aplicada, Instituto de Investigación de Navarra, Centro Investigación Biomédica en Red Cáncer (CIBERONC), Pamplona (J.S.-M.), the University Hospi, Dominik Dytfeld, Surbhi Sidana, Luciano J Costa, Albert Oriol, Rakesh Popat, Abdullah M Khan, Yaël C Cohen, P Joy Ho, James Griffin, Nikoletta Lendvai, Carolina Lonardi, Ana Slaughter, Jordan M Schecter, Carolyn C Jackson, Kaitlyn Connors, Katherine Li, Enrique Zudaire, Diana Chen, Jane Gilbert, Tzu-Min Yeh, Sarah Nagle, Erika Florendo, Lida Pacaud, Nitin Patel, Simon J Harrison, and Hermann Einsele.
• From the Cancer Center Clínica Universidad de Navarra, Centro Investigación Medica Aplicada, Instituto de Investigación de Navarra, Centro Investigación Biomédica en Red Cáncer (CIBERONC), Pamplona (J.S.-M.), the University Hospital of Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro Investigación del Cáncer, CIBERONC, Salamanca (M.-V.M.), the Amyloidosis and Myeloma Unit, Department of Hematology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (C.F.L.), the Hematological Malignancies Clinical Research Unit, Hospital 12 de Octubre Universidad Complutense, Centro Nacional de Investigaciones Oncológicas, CIBERONC, Madrid (J.M.-L.), and the Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona (A.O.) - all in Spain; the Medical College of Wisconsin, Milwaukee (B.D.); the University College London Cancer Institute (K.Y.) and University College London Hospitals, NHS Foundation Trust (R.P.), London, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol (J. Griffin), and Janssen Research and Development, High Wycombe (J. Gilbert) - all in the United Kingdom; Monash University (A. Spencer) and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Sir Peter MacCallum Department of Oncology, University of Melbourne (S.J.H.), Melbourne, VIC, and Royal Prince Alfred Hospital and the University of Sydney, Sydney (P.J.H.) - all in Australia; the Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, and the Division of Hematology and Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem - both in Belgium (S.A.); the Department of Hematology, University Hospital Hôtel-Dieu, Nantes (P.M., C.T.), and Service d'Hématologie et Thérapie Cellulaire, Hôpital La Milétrie, and Centre d'investigation Clinique INSERM 1402, Poitiers University Hospital, Poitiers (X.L.) - both in France; Tel Aviv Sourasky Medical Center (I.A., Y.C.C.) and the Sackler Faculty of Medicine, Tel Aviv University (Y.C.C.) - both in Tel Aviv, Israel; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and the Department of Medical and Surgical Sciences, Bologna University School of Medicine, Bologna, Italy (M.C.); the Department of Hematology, Japanese Red Cross Medical Center, Tokyo (T.I.); the Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (S.J.K.); the Department of Hematology, University Medical Center Groningen, Groningen (W.R.), and Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam (N.W.C.J.D.) - both in the Netherlands; Poznan University of Medical Sciences, Poznan, Poland (D.D.); Stanford University School of Medicine, Stanford, CA (S.S.); the University of Alabama at Birmingham, Birmingham (L.J.C.); Ohio State University Comprehensive Cancer Center, Columbus (A.M.K.); Janssen Research and Development, Raritan (N.L., J.M.S., C.C.J., K.C., T.Y., S.N.), and Legend Biotech, Somerset (E.F., L.P., N.P.) - both in New Jersey; Janssen, Buenos Aires (C.L.); Cilag International, Zug, Switzerland (A. Slaughter); Janssen Research and Development, Spring House, PA (K.L., E.Z.); Janssen China Research and Development, Shanghai (D.C.); and Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, Germany (H.E.).
• N. Engl. J. Med. 2023 Jul 27; 389 (4): 335347335-347.

BackgroundCiltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease.MethodsIn this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival.ResultsA total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%).ConclusionsA single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).Copyright © 2023 Massachusetts Medical Society.

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