A landmark phase 3 trial in newly diagnosed multiple myeloma challenges a long-standing standard: indefinite lenalidomide maintenance. For patients who do not receive an autologous stem cell transplant, clinicians have often continued therapy until progression despite limited evidence on the optimal duration. The results, published in the New England Journal of Medicine, suggest that continuing lenalidomide indefinitely adds harm without improving survival.
In the ENDURANCE study (E1A11, NCT01863550), researchers compared two strategies after patients completed initial induction therapy. One group received continuous lenalidomide until disease progression, while the other stopped treatment after a fixed 2-year course. With a median follow-up of 7 years, both approaches produced nearly identical survival outcomes.
Overall survival was 69.0% in the continuous-treatment arm versus 68.6% in the limited-duration arm, indicating no survival advantage to indefinite maintenance. This finding is particularly relevant because maintenance therapy is widely viewed as a low-intensity “set and continue” option, yet it may carry cumulative toxicity and financial burden over time.
While disease control remained substantial in both groups, progression-free survival showed a modest difference. Median progression-free survival was 42.5 months with indefinite therapy and 38.9 months with limited duration, reflecting a slight trade-off in time to progression. However, the key message is that this trade-off did not translate into longer survival.
Safety and long-term risks favored the fixed-duration strategy. The 5-year cumulative incidence of second primary cancers (excluding non-melanoma skin cancer) was 11.2% for indefinite therapy versus 8.3% for limited lenalidomide. Grade 3–5 non-hematologic treatment-related toxicity was also higher with continuous treatment (23.5% vs 16.9%).
Importantly, the study included patients categorized as standard risk by biomarker testing, meaning results may inform a broad clinical segment. Investigators emphasized that maintenance therapy functions as part of everyday life for patients, and the trial directly addresses the recurring question of “how long is long enough.”
The ENDURANCE trial also integrated an initial-treatment comparison involving VRd versus KRd, with investigators reporting no change to standard initial VRd based on earlier and longer-term follow-up analyses. Funded by the National Cancer Institute and led through ECOG-ACRIN, the work was further supported by Amgen.
Overall, ENDURANCE provides evidence for a paradigm shift toward predefined maintenance durations for many myeloma patients. By reducing avoidable toxicity and potentially lowering healthcare costs, the trial may reshape future trial designs and treatment guidelines.
Subject of Research: Multiple myeloma maintenance therapy duration (lenalidomide)
Article Title: Continuous versus Fixed Duration Maintenance Therapy in Multiple Myeloma
News Publication Date: 15-Jul-2026
Web References: http://www.nejm.org/
References: Kumar SK. Lancet Oncol. August 2020; Kumar SK. J Clin Oncol. May 2025 (as cited in the provided text)
Image Credits: Mayo Clinic
Keywords: multiple myeloma; lenalidomide; maintenance therapy; phase 3 trial; ENDURANCE; progression-free survival; overall survival; toxicity; second primary cancers; ECOG-ACRIN
