In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown.
In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival.
Among 357 patients in the RVD-alone group and 365 in the transplantation group, at a median follow-up of 76.0 months, 328 events of disease progression or death occurred; the risk was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% confidence interval [CI], 1.23 to 1.91; P<0.001); median progression-free survival was 46.2 months and 67.5 months. The percentage of patients with a partial response or better was 95.0% in the RVD-alone group and 97.5% in the transplantation group (P=0.55); 42.0% and 46.8%, respectively, had a complete response or better (P=0.99). Treatment-related adverse events of grade 3 or higher occurred in 78.2% and 94.2%, respectively; 5-year survival was 79.2% and 80.7% (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65).
Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION ClinicalTrials.gov number, NCT01208662.)
Funding and Disclosures
Supported by grants from the
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Drs. K. Anderson and Munshi contributed equally to this article.
The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
This article was published on June 5, 2022, at NEJM.org.
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
We thank all the patients and their families for their participation in the trial; all the investigators, clinical research coordinators, nursing teams, and administrative staff at all the trial sites; the following persons for their contributions: Steve Hill, Ph.D., of Ashfield MedComms, an Ashfield Health company, for medical writing and editing assistance with an earlier version of the manuscript; the data and safety monitoring committee (Joan Bladé, M.D., Robert Kyle, M.D., Christian Straaker, M.D., Ralph D’Agostino, Ph.D., Joe Massarro, Ph.D., and Jean Pearlstein, B.A.); Jack Sparacino, B.S., and Ashley Ford, B.A., for administrative assistance to the response review committee; the steering committee (George Canellos, M.D., and the late Bertrand Coiffier, M.D., Ph.D.); the contract research organization CRA Solutions (especially Kellie Hill, Pharm.D.); Jean-Luc Harousseau, M.D., for assistance and mentorship; our pharmaceutical industry partners for their assistance, including Dixie-Lee Esseltine, M.D., formerly of Millennium Pharmaceuticals–Takeda Pharmaceuticals, Mark Williamson, B.S., Mei-Ling Smith, M.S.N., N.P., and Barbara Franklin, M.S., of Millennium Pharmaceuticals–Takeda Pharmaceuticals, Mark Alles, M.B.A., Mohammed Hussain, M.D., Thomas Cavanaugh, B.A., and Amit Agrawal, M.D., Ph.D., formerly of Celgene–Bristol Myers Squibb, and Michael Sturniolo, Ph.D., Bruno Costa, M.Sc., and Phenoia Browne, M.B.A., of Celgene–Bristol Myers Squibb; Anne T. Farrell, M.D., for guidance and assistance; the late Robert C. Kane, M.D., of the Food and Drug Administration, for the development of the protocol and conduct of the trial; the Blood and Marrow Transplant Clinical Trials Network for vital assistance; and the Alliance for Clinical Trials in Oncology for their endorsement.
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