• Pieter Sonneveld, Meletios A Dimopoulos, Mario Boccadoro, Hang Quach, P Joy Ho, Meral Beksac, Cyrille Hulin, Elisabetta Antonioli, Xavier Leleu, Silvia Mangiacavalli, Aurore Perrot, Michele Cavo, Angelo Belotti, Annemiek Broijl, Francesca Gay, Roberto Mina, Inger S Nijhof, van de DonkNiels W C JNWCJFrom Erasmus MC Cancer Institute, Rotterdam (P.S., A. Broijl, S.L.), the Department of Hematology, Amsterdam University Medical Center and Vrije Universiteit Amsterdam, Amsterdam (I.S.N., N.W.C.J.D.), the Department of Hematology, Eirini Katodritou, Fredrik Schjesvold, Anna Sureda Balari, Laura Rosiñol, Michel Delforge, Wilfried Roeloffzen, Tobias Silzle, Annette Vangsted, Hermann Einsele, Andrew Spencer, Roman Hajek, Artur Jurczyszyn, Sarah Lonergan, Tahamtan Ahmadi, Yanfang Liu, Jianping Wang, Diego Vieyra, Emilie M J van Brummelen, Veronique Vanquickelberghe, Anna Sitthi-Amorn, Carla J de Boer, Robin Carson, Paula Rodriguez-Otero, Joan Bladé, Philippe Moreau, and PERSEUS Trial Investigators.
• From Erasmus MC Cancer Institute, Rotterdam (P.S., A. Broijl, S.L.), the Department of Hematology, Amsterdam University Medical Center and Vrije Universiteit Amsterdam, Amsterdam (I.S.N., N.W.C.J.D.), the Department of Hematology, St. Antonius Hospital, Nieuwegein (I.S.N.), University Medical Center Groningen, Groningen (W.R.), and Janssen Research and Development, Leiden (E.M.J.B., C.J.B.) - all in the Netherlands; National and Kapodistrian University of Athens, Athens (M.A.D.), and the Department of Hematology, Theagenion Cancer Hospital, Thessaloniki (E.K.) - both in Greece; the Myeloma Unit, Division of Hematology, University of Turin and Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino (M. Boccadoro), the Division of Hematology 1, AOU Città della Salute e della Scienza di Torino (F.G., R.M.), and the Department of Molecular Biotechnology and Health Sciences, University of Turin (F.G., R.M.), Turin, the Department of Hematology, Careggi Hospital and University of Florence, Florence (E.A.), the Division of Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia (S.M.), IRCCS AOU di Bologna, Istituto di Ematologia "Seràgnoli," and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna (M.C.), and the Department of Hematology, Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia, Brescia (A. Belotti) - all in Italy; the University of Melbourne and St. Vincent's Hospital, Melbourne, VIC (H.Q.), the Institute of Haematology, Royal Prince Alfred Hospital and University of Sydney, Camperdown, NSW (P.J.H.), and the Malignant Haematology and Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne, VIC (A.S.) - all in Australia; Ankara University, Ankara, Turkey (M. Beksac); the Department of Hematology, Hôpital Haut Lévêque, University Hospital, Pessac (C.H.), the University of Poitiers, Centre Hospitalier Universitaire (CHU) and INSERM 1313, Poitiers (X.L.), CHU de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, Université de Toulouse, Université Paul Sabatier, Service d'Hématologie, Toulouse (A.P.), and the Hematology Department, University Hospital Hôtel-Dieu, Nantes (P.M.) - all in France; Oslo Myeloma Center, Department of Hematology, Oslo University Hospital, and KG Jebsen Center for B-cell Malignancies, University of Oslo - both in Oslo (F.S.); the Hematology Department, Institut Català d'Oncologia-Hospitalet, Instituto de Investigación Biomédica de Bellvitge (A.S.B.), University of Barcelona (A.S.B.), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (L.R., J.B.), and Grupo Español de Mieloma-Programa Español de Tratamientos en Hematología (J.B.), Barcelona, and the Department of Hematology, Cancer Center Clínica Universidad de Navarra, Pamplona (P.R.-O.) - all in Spain; the University of Leuven, Leuven (M.D.), and Janssen Research and Development, Beerse (V.V.) - both in Belgium; the Department of Medical Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (T.S.); the Department of Hematology, Rigshospitalet, Copenhagen (A.V.); the Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany (H.E.); the Department of Hemato-oncology, University Hospital Ostrava, and the Faculty of Medicine, University of Ostrava - both in Ostrava, Czech Republic (R.H.); the Plasma Cell Dyscrasias Center, Department of Hematology, Jagiellonian University Medical College, Kraków, Poland (A.J.); Genmab US, Plainsboro, NJ (T.A.); Janssen Research and Development, Beijing (Y.L.); and Janssen Research and Development, Spring House, PA (J.W., D.V., A.S.-A., R.C.).
• N. Engl. J. Med. 2024 Jan 25; 390 (4): 301313301-313.

BackgroundDaratumumab, a monoclonal antibody targeting CD38, has been approved for use with standard myeloma regimens. An evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients with newly diagnosed multiple myeloma is needed.MethodsIn this phase 3 trial, we randomly assigned 709 transplantation-eligible patients with newly diagnosed multiple myeloma to receive either subcutaneous daratumumab combined with VRd induction and consolidation therapy and with lenalidomide maintenance therapy (D-VRd group) or VRd induction and consolidation therapy and lenalidomide maintenance therapy alone (VRd group). The primary end point was progression-free survival. Key secondary end points were a complete response or better and minimal residual disease (MRD)-negative status.ResultsAt a median follow-up of 47.5 months, the risk of disease progression or death in the D-VRd group was lower than the risk in the VRd group. The estimated percentage of patients with progression-free survival at 48 months was 84.3% in the D-VRd group and 67.7% in the VRd group (hazard ratio for disease progression or death, 0.42; 95% confidence interval, 0.30 to 0.59; P<0.001); the P value crossed the prespecified stopping boundary (P = 0.0126). The percentage of patients with a complete response or better was higher in the D-VRd group than in the VRd group (87.9% vs. 70.1%, P<0.001), as was the percentage of patients with MRD-negative status (75.2% vs. 47.5%, P<0.001). Death occurred in 34 patients in the D-VRd group and 44 patients in the VRd group. Grade 3 or 4 adverse events occurred in most patients in both groups; the most common were neutropenia (62.1% with D-VRd and 51.0% with VRd) and thrombocytopenia (29.1% and 17.3%, respectively). Serious adverse events occurred in 57.0% of the patients in the D-VRd group and 49.3% of those in the VRd group.ConclusionsThe addition of subcutaneous daratumumab to VRd induction and consolidation therapy and to lenalidomide maintenance therapy conferred a significant benefit with respect to progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma. (Funded by the European Myeloma Network in collaboration with Janssen Research and Development; PERSEUS ClinicalTrials.gov number, NCT03710603; EudraCT number, 2018-002992-16.).Copyright © 2023 Massachusetts Medical Society.

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