Indefinite Lenalidomide Maintenance Fails to Improve Overall Survival in Standard-Risk Multiple Myeloma
Results from the Phase 3 ENDURANCE Trial
Results from the Phase 3 ENDURANCE Trial
Clinical Summary:
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Design/Population: The phase 3 ENDURANCE trial compared indefinite-duration versus fixed-duration (2-year) lenalidomide maintenance therapy in patients with standard-risk newly diagnosed multiple myeloma who did not undergo upfront autologous stem-cell transplantation following induction with a proteasome inhibitor–lenalidomide regimen.
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Key Outcomes: Indefinite-duration lenalidomide did not improve overall survival compared with 2 years of maintenance therapy after a median follow-up of 86 months. Although progression-free survival numerically favored indefinite therapy, longer treatment was associated with higher rates of grade ≥3 adverse events and second primary malignancies.
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Clinical Relevance: These findings suggest that extending lenalidomide maintenance beyond 2 years does not improve overall survival in standard-risk transplant-ineligible multiple myeloma and may increase treatment-related toxicity, supporting consideration of fixed-duration maintenance in appropriately selected patients.
Results from the phase 3 ENDURANCE trial demonstrated that indefinite-duration lenalidomide maintenance therapy did not improve overall survival (OS) compared with 2 years of maintenance therapy in patients with standard-risk newly diagnosed multiple myeloma who did not undergo upfront autologous stem-cell transplantation, supporting fixed-duration treatment as a potential alternative for selected patients.
According to Shaji Kumar, MD, Mayo Clinic, Rochester, Minnesota, and coauthors, “current treatment of newly diagnosed multiple myeloma involves lenalidomide maintenance therapy given until disease progression…. [However] the appropriate duration of maintenance therapy with lenalidomide has been unclear.”
In this phase 3 trial, 516 patients with standard-risk newly diagnosed multiple myeloma who completed induction therapy with a proteasome inhibitor–lenalidomide regimen were randomized to receive either indefinite-duration lenalidomide maintenance (n = 260) or fixed-duration lenalidomide maintenance for 2 years (n = 256). The primary end point was OS. Secondary end points included progression-free survival (PFS), incidence of second primary malignancies, and safety.
After a median follow-up of 86 months, OS did not differ significantly between treatment groups. The 7-year OS rate was 68.6% in the indefinite-duration arm and 69% in the fixed-duration arm (difference, –0.4 percentage points; P = .93). Seven-year PFS rates were 36.1% and 29.7%, respectively.
Longer maintenance therapy was associated with greater toxicity. The 5-year cumulative incidence of second primary malignancies, excluding non-melanoma skin cancer, was 11.2% with indefinite-duration lenalidomide compared with 8.3% with fixed-duration therapy. Grade ≥3 non-hematologic adverse events occurred in 48.2% and 31.5% of patients, respectively.
“Indefinite-duration maintenance therapy after induction therapy did not result in significantly longer [OS] than fixed-duration maintenance therapy,” concluded Dr Kumar et al.
Source:
Kumar S, Jacobus S, Cohen A, et al. Continuous or fixed-duration maintenance therapy in multiple myeloma. N Engl J Med. Published online: July 15, 2026. doi: 10.1056/NEJMoa2600157
