Study Finds Better Outcome With Melphalan Plus ASCT vs Chemotherapy Plus Lenalidomide Consolidation in Multiple Myeloma
In a phase III trial reported in The Lancet Oncology, Gay et al found that progression-free survival was shorter with lenalidomide (Revlimid) plus chemotherapy vs high-dose melphalan plus autologous stem cell transplantation in transplant-eligible patients with multiple myeloma, with no significant difference noted for maintenance with lenalidomide plus prednisone vs lenalidomide alone.
Study Details
In the open-label, partial 2 x 2 factorial trial, 389 patients were enrolled between July 2009 and May 2011 from 59 sites in Australia, the Czech Republic, and Italy. Patients received induction therapy with four 28-day cycles of lenalidomide (25 mg on days 1–21) and dexamethasone (40 mg on days 1, 8, 15, and 22) and subsequent chemotherapy with cyclophosphamide (3 g/m2) followed by granulocyte colony-stimulating factor.
Patients were randomly assigned to receive consolidation therapy with either chemotherapy plus lenalidomide (six cycles of cyclophosphamide at 300 mg/m2 on days 1, 8, and 15; dexamethasone at 40 mg on days 1, 8, 15, and 22; and lenalidomide at 25 mg on days 1–21) or two courses of high-dose melphalan (200 mg/m2) and autologous stem cell transplantation and maintenance therapy with lenalidomide (10 mg on days 1–21) plus prednisone (50 mg every other day) or lenalidomide alone.
Overall, 256 patients were eligible for consolidation therapy (127 with high-dose melphalan and autologous stem cell transplantation and 129 with chemotherapy plus lenalidomide). A total of 223 were eligible for maintenance therapy (117 with lenalidomide plus prednisone and 106 with lenalidomide alone).
Progression-Free and Overall Survival
Median follow-up was 52.0 months. Median progression-free survival, the primary endpoint of the study, was 28.6 months with chemotherapy plus lenalidomide consolidation vs 43.3 months with high-dose melphalan plus autologous stem cell transplantation (hazard ratio [HR] for the first 24 months = 2.51, P < .0001). Median progression-free survival with maintenance therapy was 37.5 months with lenalidomide plus prednisone vs 28.5 months with lenalidomide alone (HR = 0.84, P = .34).
At 4 years, overall survival was 86% with melphalan plus autologous stem cell transplantation vs 73% with chemotherapy plus lenalidomide (HR = 2.40, P = .004).
Toxicities
Patients in the chemotherapy plus lenalidomide group had a lower frequency of grade 3 or 4 adverse events, including hematologic events (26% vs 84%), gastrointestinal events (5% vs 20%), and infection (5% vs 19%). There was no marked difference between the maintenance lenalidomide and lenalidomide plus prednisone groups in terms of toxicity, with the most common grade 3 or 4 adverse events being neutropenia (13% vs 8%), infection (5% vs 8%), and systemic toxicities (2% vs 6%).
The investigators concluded: “Consolidation with high-dose melphalan and ASCT remains the preferred option in transplant-eligible patients with multiple myeloma, despite a better toxicity profile with chemotherapy plus lenalidomide.”
The study was funded by Celgene.
Antonio Palumbo, MD, of the University of Torino, Turin, Italy, is the corresponding author of The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
