ENDURANCE Trial Questions Need for Indefinite Lenalidomide Maintenance in Multiple Myeloma

By: Julia Cipriano, MS, CMPP
Posted: Friday, August 14, 2026

In the phase III ENDURANCE trial, indefinite-duration lenalidomide maintenance therapy after induction did not significantly improve overall survival compared with fixed-duration maintenance therapy among patients with standard-risk, newly diagnosed multiple myeloma who did not undergo upfront autologous stem cell transplantation. The findings were published by Shaji Kumar, MD, of Mayo Clinic, Rochester, Minnesota, and colleagues in The New England Journal of Medicine.

“Current treatment of newly diagnosed multiple myeloma involves lenalidomide maintenance therapy given until disease progression,” the investigators explained. However, “the appropriate duration of maintenance therapy with lenalidomide has been unclear,” providing the rationale for the trial.

After induction treatment with a proteasome inhibitor–lenalidomide combination, patients with standard-risk, newly diagnosed multiple myeloma who were not undergoing upfront autologous stem cell transplantation were randomly assigned to receive indefinite-duration (continuous; n = 260) or fixed-duration (for 2 years; n = 256) maintenance therapy with lenalidomide. Overall survival was evaluated as the primary endpoint.

After a median follow-up of 86 months, overall survival did not appear to significantly differ between the indefinite- and fixed-duration treatment groups. Overall survival at 7 years was 68.6% with indefinite-duration lenalidomide and 69.0% with fixed-duration treatment, with 80 deaths reported in each group (difference = −0.4 percentage points; P = .93). The 7-year progression-free survival rates were 36.1% and 29.7%, respectively (difference = 6.4 percentage points).

Second primary cancers, excluding nonmelanoma skin cancer, occurred at a 5-year cumulative incidence of 11.2% with indefinite-duration lenalidomide and 8.3% with the fixed-duration schedule. The incidence of grade 3 or higher nonhematologic adverse events was higher with indefinite-duration lenalidomide (48.2% vs 31.5%).

Disclosure: For full disclosures of the study authors, visit nejm.org.

The New England Journal of Medicine

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