Melphalan/prednisone/lenalidomide (MPR) versus high-dose melphalan and autologous transplantation (MEL200) in newly diagnosed multiple myeloma (MM) patients: A phase III trial.

Abstract

8020 Background: The introduction of novel agents questions the role of autologous stem-cell transplantation (ASCT). This is the first prospective randomized study comparing conventional chemotherapy plus novel agents (MPR) with tandem high-dose melphalan (MEL200) and ASCT in newly diagnosed MM patients (Pts). Methods: All pts (N=402) received four 28-day cycles of lenalidomide (25 mg, d1-21) and low-dose dexamethasone (40 mg, d1,8,15,22) (Rd) as induction. Pts (N=202) were then randomized to MPR [six 28-day cycles of melphalan (0.18 mg/kg d1-4), prednisone (2 mg/kg d1-4) and lenalidomide (10 mg d1-21); pts (N=200)] or MEL200 (tandem melphalan 200 mg/m2 with stem-cell support). Primary end point was PFS. Results: Response rates were similar in the two groups (MPR vs MEL200): ≥ VGPR (60% vs. 58%, p=0.24) and CR (20% vs. 25% p=0.49). After a median follow-up of 20 months, the 18-months PFS was 68% in MPR and 78% in MEL200 (HR=0.58, p=0.006). CR prolonged the 18-months PFS in the MPR (90% vs 66%) and in the MEL200 group (87% vs 76%). The 18-months OS was similar (91% vs 95%; p=0.073). In the MPR and MEL200 groups, G3-4 neutropenia was 55% vs 89% (p <.001); G3-4 infections were 0% vs 17% (p <.001); G3-4 gastrointestinal toxicity was 0% vs. 21% (p<.001); DVT was 2.44% vs 1.13% (p=0.43); second tumors were 0.005% in both arms. Conclusions: MEL200 was superior to MPR for PFS, although toxicities were significantly higher. This is the first report showing a PFS advantage for ASCT in comparison with combinations including novel agents. At present OS is not significantly different in the two groups.