Autologous Transplantation and Maintenance Therapy in Multiple Myeloma

TLDR

In a phase‑3, open‑label randomized trial, 273 patients ≤65 years received either high‑dose melphalan plus autologous stem‑cell transplantation or melphalan‑prednisone‑lenalidomide consolidation, and 251 patients were randomized to lenalidomide maintenance or no maintenance, with progression‑free survival as the primary endpoint and a median follow‑up of 51.2 months. High‑dose melphalan plus transplantation yielded a median PFS of 43.0 months versus 22.4 months for MPR (HR 0.44) and improved 4‑year OS (81.6 % vs 65.3 %, HR 0.55); lenalidomide maintenance extended median PFS to 41.9 months versus 21.6 months (HR 0.47) but did not significantly affect 3‑year OS, with higher rates of grade 3/4 neutropenia, GI events, and infections in the transplant arm and more neutropenia and dermatologic toxicity with maintenance. The study was funded by Celgene and registered under ClinicalTrials.gov NCT00551928.

Abstract

This open-label, randomized, phase 3 study compared melphalan at a dose of 200 mg per square meter of body-surface area plus autologous stem-cell transplantation with melphalan-prednisone-lenalidomide (MPR) and compared lenalidomide maintenance therapy with no maintenance therapy in patients with newly diagnosed multiple myeloma.We randomly assigned 273 patients 65 years of age or younger to high-dose melphalan plus stem-cell transplantation or MPR consolidation therapy after induction, and 251 patients to lenalidomide maintenance therapy or no maintenance therapy. The primary end point was progression-free survival.The median follow-up period was 51.2 months. Both progression-free and overall survival were significantly longer with high-dose melphalan plus stem-cell transplantation than with MPR (median progression-free survival, 43.0 months vs. 22.4 months; hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.32 to 0.61; P<0.001; and 4-year overall survival, 81.6% vs. 65.3%; hazard ratio for death, 0.55; 95% CI, 0.32 to 0.93; P=0.02). Median progression-free survival was significantly longer with lenalidomide maintenance than with no maintenance (41.9 months vs. 21.6 months; hazard ratio for progression or death, 0.47; 95% CI, 0.33 to 0.65; P<0.001), but 3-year overall survival was not significantly prolonged (88.0% vs. 79.2%; hazard ratio for death, 0.64; 95% CI, 0.36 to 1.15; P=0.14). Grade 3 or 4 neutropenia was significantly more frequent with high-dose melphalan than with MPR (94.3% vs. 51.5%), as were gastrointestinal adverse events (18.4% vs. 0%) and infections (16.3% vs. 0.8%); neutropenia and dermatologic toxic effects were more frequent with lenalidomide maintenance than with no maintenance (23.3% vs. 0% and 4.3% vs. 0%, respectively).Consolidation therapy with high-dose melphalan plus stem-cell transplantation, as compared with MPR, significantly prolonged progression-free and overall survival among patients with multiple myeloma who were 65 years of age or younger. Lenalidomide maintenance, as compared with no maintenance, significantly prolonged progression-free survival. (Funded by Celgene; ClinicalTrials.gov number, NCT00551928.).