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 transplan- tation with melphalan–prednisone–lenalidomide (MPR) and compared lenalidomide maintenance therapy with no maintenance therapy in patients with newly diag- nosed multiple myeloma.
We randomly assigned 273 patients 65 years of age or younger to high-dose mel- phalan 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 trans- plantation 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 sig- nificantly 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. Le- nalidomide maintenance, as compared with no maintenance, significantly prolonged progression-free survival. (Funded by Celgene; ClinicalTrials.gov number, NCT00551928.)