Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma

Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma Published July 15, 2026 N Engl J Med 2026;395:221-232 DOI: 10.1056/NEJMoa2600157 Abstract Background Current treatment of newly diagnosed multiple myeloma involves lenalidomide maintenance therapy given until disease progression. The appropriate duration of maintenance therapy with lenalidomide has been unclear. Methods In this phase 3 trial, we enrolled patients with standard-risk newly diagnosed multiple myeloma who were not undergoing up-front autologous stem-cell transplantation. After induction treatment with a proteasome inhibitor–lenalidomide combination, patients were randomly assigned to receive indefinite-duration (continuous) lenalidomide or fixed-duration lenalidomide (for 2 years). The primary end point was overall survival; the trial had 80% power to detect a 50% increase in median survival (from 5 years to 7.5 years), with a two-sided alpha level of 5%, 395 patients undergoing randomization, and 204 deaths occurring during 9 years of follow-up. Results At the end of induction, 516 patients were randomly assigned to the indefinite-duration group (260 patients) or the fixed-duration group (256 patients). At a median follow-up of 86 months, overall survival did not differ significantly between the groups. With 80 deaths in each group, overall survival at 7 years was 68.6% in the indefinite-duration group and 69.0% in the fixed-duration group (difference, −0.4 percentage points; 95 confidence interval [CI], −9.0 to 8.3; P=0.93). Progression-free survival at 7 years was 36.1% in the indefinite-duration group and 29.7% in the fixed-duration group (difference, 6.4 percentage points; 95% CI, −2.6 to 15.4). The 5-year cumulative incidence of second primary cancers, excluding nonmelanoma skin cancer, was 11.2% with indefinite-duration lenalidomide and 8.3% with fixed-duration lenalidomide. More adverse events occurred with indefinite-duration lenalidomide; the incidence of nonhematologic events of grade 3 or higher was 48.2% with indefinite-duration therapy and 31.5% with fixed-duration therapy. Conclusions In this phase 3 trial involving patients with standard-risk newly diagnosed multiple myeloma who were not undergoing up-front autologous stem-cell transplantation, indefinite-duration maintenance therapy after induction therapy did not result in significantly longer overall survival than fixed-duration maintenance therapy. (Funded by the National Cancer Institute of the National Institutes of Health and Amgen; ENDURANCE ClinicalTrials.gov number, NCT01863550.) Are you a member of an institution such as a university or hospital?Learn more about Institutional Access Notes 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. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. Supported by the National Cancer Institute, National Institutes of Health (award numbers, U10CA180820, U10CA180794, UG1CA189828, UG1CA232760, UG1CA189956, UG1CA189825, UG1CA233277, UG1CA189863, U10CA180888, UG1CA233337, UG1CA189821, U10CA180821, UG1CA189858, UG1CA189956, UG1CA189971, UG1CA189830, UG1CA233340, UG1CA233163, UG1CA189957, UG1CA233247, UG1CA233180, and UG1CA233329), and by Amgen. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank the patients who volunteered to participate in this trial, their families, and the staff members at the trial sites who cared for them. Supplementary Material Information & Authors Information Published In Copyright Copyright © 2026 Massachusetts Medical Society. All rights reserved. For personal use only. Any commercial reuse of NEJM Group content requires permission. History Published online: July 15, 2026 Published in issue: July 16, 2026 Topics Authors Metrics & Citations Metrics Altmetrics Citations Export citation Select the format you want to export the citation of this publication. Cited by - Time to Stop? Rethinking the Duration of Maintenance Treatment in Multiple Myeloma, New England Journal of Medicine, 395, 3, (302-303), (2026)./doi/full/10.1056/NEJMe2604761 Loading...