• Thierry Facon, Meletios-Athanasios Dimopoulos, Xavier P Leleu, Meral Beksac, Ludek Pour, Roman Hájek, Zhuogang Liu, Jiri Minarik, Philippe Moreau, Joanna Romejko-Jarosinska, Ivan Spicka, Vladimir I Vorobyev, Britta Besemer, Tadao Ishida, Wojciech Janowski, Sevgi Kalayoglu-Besisik, Gurdeep Parmar, Pawel Robak, Elena Zamagni, Hartmut Goldschmidt, Thomas G Martin, Salomon Manier, Mohamad Mohty, Corina Oprea, Marie-France Brégeault, Sandrine Macé, Christelle Berthou, David Bregman, Zandra Klippel, Robert Z Orlowski, and IMROZ Study Group.
• From the Department of Hematology, Centre Hospitalier Universitaire (CHU) de Lille, University of Lille, Lille (T.F., S. Manier), the French National Academy of Medicine (T.F.), and the Department of Hematology, Hôpital Saint-Antoine, Sorbonne University and INSERM (M.M.), Paris, Service d'Hématologie et Thérapie Cellulaire, CHU and Centre d'Investigation Clinique INSERM Unité 1402, Poitiers (X.P.L.), the Department of Hematology, University Hospital Hôtel-Dieu, Nantes (P.M.), and Sanofi, Research and Development, Vitry-sur-Seine (C.O., M.-F.B., S. Macé, C.B.) - all in France; the Plasma Cell Dyscrasia Unit, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens (M.-A.D.); the Department of Hematology, Ankara University, and the Istinye University Ankara Liv Hospital, Ankara (M.B.), and the Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul (S.K.-B.) - all in Turkey; the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the Department of Hemato-Oncology, University Hospital Ostrava, and the Faculty of Medicine, University of Ostrava, Ostrava (R.H.), the Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University and University Hospital Olomouc, Olomouc (J.M.), and the Charles University and General Hospital in Prague, Prague (I.S.) - all in the Czech Republic; Shengjing Hospital of China Medical University, Shenyang, China (Z.L.); the Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw (J.R.-J.), and the Department of General Hematology, Copernicus Memorial Hospital, Comprehensive Cancer Center and Traumatology, Łódź (P.R.) - both in Poland; the S.P. Botkin Moscow City Clinical Hospital, Moscow (V.I.V.); the Department of Hematology, Oncology, Immunology, and Rheumatology, University Hospital of Tübingen, Tübingen (B.B.), and the Department of Internal Medicine V, University of Heidelberg, Heidelberg (H.G.) - both in Germany; the Japanese Red Cross Medical Center, Tokyo (T.I.); Calvary Mater Newcastle, Newcastle, NSW (W.J.), and the Illawarra Cancer Care Centre, Wollongong, NSW (G.P.) - both in Australia; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli," and Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy (E.Z.); the Division of Hematology-Oncology, University of California, San Francisco, San Francisco (T.G.M.); Sanofi, Patient Safety and Pharmacovigilance, Bridgewater, NJ (D.B.); Sanofi, Cambridge, MA (Z.K.); and the Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, Houston (R.Z.O.).
• N. Engl. J. Med. 2024 Oct 31; 391 (17): 159716091597-1609.

BackgroundBortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantation is unclear.MethodsIn an international, open-label, phase 3 trial, we randomly assigned, in a 3:2 ratio, patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation to receive either isatuximab plus VRd or VRd alone. The primary efficacy end point was progression-free survival. Key secondary end points included a complete response or better and minimal residual disease (MRD)-negative status in patients with a complete response.ResultsA total of 446 patients underwent randomization. At a median follow-up of 59.7 months, the estimated progression-free survival at 60 months was 63.2% in the isatuximab-VRd group, as compared with 45.2% in the VRd group (hazard ratio for disease progression or death, 0.60; 98.5% confidence interval, 0.41 to 0.88; P<0.001). The percentage of patients with a complete response or better was significantly higher in the isatuximab-VRd group than in the VRd group (74.7% vs. 64.1%, P = 0.01), as was the percentage of patients with MRD-negative status and a complete response (55.5% vs. 40.9%, P = 0.003). No new safety signals were observed with the isatuximab-VRd regimen. The incidence of serious adverse events during treatment and the incidence of adverse events leading to discontinuation were similar in the two groups.ConclusionsIsatuximab-VRd was more effective than VRd as initial therapy in patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation. (Funded by Sanofi and a Cancer Center Support Grant; IMROZ ClinicalTrials.gov number, NCT03319667.).Copyright © 2024 Massachusetts Medical Society.

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