ENDURANCE trial: two-year lenalidomide matches lifelong therapy

The randomised phase III ENDURANCE trial has found that two years of lenalidomide maintenance therapy delivers the same overall survival as continuous treatment until disease progression in patients with standard-risk multiple myeloma, according to results published in the New England Journal of Medicine on 15 July 2026.

The study, designed and conducted by the ECOG-ACRIN Cancer Research Group, enrolled 516 patients who had completed initial treatment but were not candidates for upfront stem cell transplantation. After nearly seven years of follow-up, overall survival was virtually identical between groups: 68.6 per cent in the indefinite-treatment arm versus 69.0 per cent in the two-year limited-duration arm.

Trial findings

Patients receiving indefinite lenalidomide experienced higher rates of fatigue, anaemia, and diarrhoea compared with those who stopped at two years. The trial also recorded a slightly higher incidence of second primary cancers over five years in the continuous-therapy group, reinforcing concerns that have accompanied long-term immunomodulatory drug use.

Lead author Dr Shaji Kumar, co-chair of the ECOG-ACRIN Myeloma Committee and a member of the International Myeloma Foundation's Scientific Advisory Board, said the results resolve a longstanding clinical question. "Our trial results show that two years is sufficient and that continuing the drug longer adds toxicity without extending life," he said.

Senior author Dr S. Vincent Rajkumar, chair of the ECOG-ACRIN Myeloma Committee and IMF Board Chairperson, said the findings support a fixed-duration standard of care for standard-risk patients, with the option to reintroduce lenalidomide or newer agents if the disease returns. Co-author Dr Sagar Lonial, IMF Vice Chairperson, described this as the first randomised trial to demonstrate non-inferiority of limited-duration maintenance in the non-transplant, triplet-induction setting.

Market and clinical context

Lenalidomide, marketed by Bristol Myers Squibb as Revlimid, has long been the backbone of myeloma maintenance, and its use until progression has been the dominant standard of care in many markets. The ENDURANCE findings are likely to prompt guideline revisions from bodies such as the National Comprehensive Cancer Network and the European Haematology Association, with clinicians in both transplant-ineligible and broader myeloma populations watching closely.

The results also carry financial implications. Indefinite lenalidomide use represents a substantial cost to health systems and patients, and a two-year stopping rule could reduce cumulative drug expenditure significantly, a point of increasing relevance as biosimilar lenalidomide competition intensifies following patent expiry. For patients, the quality-of-life benefit of a defined treatment end-point is considerable: fewer side effects, reduced monitoring burden, and greater certainty about their care pathway.

The myeloma treatment landscape continues to evolve rapidly, with bispecific antibodies and CAR-T therapies generating strong clinical data in relapsed and refractory settings. ENDURANCE adds an important piece to the earlier-line picture by clarifying how long existing standard-of-care agents need to be used, potentially freeing clinical bandwidth and patient capacity for earlier adoption of novel agents at relapse. The trial was funded by the US National Institutes of Health and the National Cancer Institute, with additional support from Amgen.