ENDURANCE Tests Lenalidomide Maintenance Duration

Indefinite lenalidomide maintenance therapy did not significantly improve overall survival compared with treatment for a fixed duration of 2 years among patients with standard-risk, newly diagnosed multiple myeloma who were not undergoing upfront autologous stem-cell transplantation. The phase 3 ENDURANCE trial was published in The New England Journal of Medicine.

The trial enrolled patients who had received induction therapy with a proteasome inhibitor–lenalidomide combination. At the end of induction, 516 patients were randomly assigned to receive lenalidomide indefinitely until disease progression or for a fixed duration of 2 years. The indefinite-duration and fixed-duration groups included 260 and 256 patients, respectively. The primary endpoint was overall survival.

After a median follow-up of 86 months, 80 deaths had occurred in each treatment group. Overall survival at 7 years was 68.6% with indefinite-duration maintenance and 69.0% with fixed-duration maintenance, representing a difference of −0.4 percentage points (95% confidence interval [CI], −9.0 to 8.3; P=.93).

Progression-free survival at 7 years was 36.1% with indefinite therapy and 29.7% with fixed-duration therapy, a difference of 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% and 8.3%, respectively. Nonhematologic adverse events of grade 3 or higher occurred in 48.2% of patients receiving indefinite therapy and 31.5% receiving fixed-duration therapy.

The investigators concluded that indefinite maintenance did not produce significantly longer overall survival than 2 years of maintenance in the population studied. The findings apply specifically to patients with standard-risk disease who did not undergo upfront autologous stem-cell transplantation.

Source: Kumar S, Jacobus S, Cohen A, et al. Continuous or fixed-duration maintenance therapy in multiple myeloma. N Engl J Med. 2026;395(3):221-232. doi:10.1056/NEJMoa2600157