PURPOSE For multiple myeloma (MM), high-dose chemotherapy and autologous blood stem-cell transplantation (ASCT) followed by lenalidomide maintenance (LenMT) at 10-15 mg/day is considered standard of care. However, dose reductions due to side effects are common and median LenMT doses achieved over time may remain lower. Dose response during LenMT has never been investigated. PATIENTS AND METHODS In a multicenter, randomized,
open-label trial, MM patients after ASCT and high-dose lenalidomide consolidation therapy (CT) at 25 mg/day were randomized to receive LenMT at either 25 or 5 mg/day. Primary endpoint was progression-free survival (PFS). RESULTS Ninety-four patients (median age 58 years) were randomized to either arm, with 22% having ISS stage 3 and 22% being in complete remission (CR). After median follow-up of 46.7 months, median doses of 14.5 and 5 mg/day were achieved in the two arms; 53% of dose reductions occurring during CT. In the high and the low dose arm, median PFS was 44.8 and 33.0 months (HR 0.65, 95%CI: 0.44-0.97; p=0.032), 36% and 23% of patients had stringent CR as best response (p=0.08), and 4-year OS was 79% and 67% (p=0.16), respectively. Hematologic toxicity, grade =3 neutropenia, and infections were initially more common with LenMT 25 mg, but decreased after dose-adjustments. SPM incidence and QoL scores in both arms were similar. CONCLUSIONS LenMT dose correlated with efficacy and toxicity. High rates of dose reductions during CT argue against a high starting dose. However, continuous up- and down-titration for each patient to the current maximum tolerated dose is prudent.