Multicenter phase 3 trial of fixed-duration versus continuous lenalidomide maintenance therapy in multiple myeloma

Current treatment of newly diagnosed multiple myeloma (NDMM) involves lenalidomide maintenance therapy given until disease progression. The multicenter phase 3 ENDURANCE trial compared overall survival (primary endpoint) after indefinite-duration lenalidomide or fixed-duration lenalidomide (for 2 years). The trial included standard-risk NDMM patients who were not undergoing upfront autologous stem-cell transplantation (ASCT). After induction treatment with a proteasome inhibitor-lenalidomide treatment, patients were randomized to the indefinite-duration group (n=260) or the fixed-duration group (n=256). At a median follow-up of 86 months, OS did not differ significantly between the groups. With 80 deaths in each group, OS rate at 7 years was 68.6% in the indefinite-duration group and 69.0% in the fixed-duration group (p=0.93); progression-free survival rate at 7 years was 36.1% versus 29.7% (difference 6.4 percentage point; 95% CI -2.6 to 15.4). The 5-year cumulative incidence of second primary cancers, excluding nonmelanoma skin cancer, was 11.2% with indefinite-duration lenalidomide and 8.3% with fixed-duration lenalidomide. The incidence of nonhematologic events of grade 3 or higher was 48.2% with indefinite-duration therapy versus 31.5% with fixed-duration therapy. The authors conclude that in this trial involving patients with standard-risk NDMM who were not undergoing upfront ASCT, indefinite-duration maintenance therapy after induction therapy did not result in significantly longer OS then fixed-duration maintenance therapy.