Trial of Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma
In a phase III trial reported in the Journal of Clinical Oncology, Stadtmauer and colleagues found that second autologous hematopoietic cell transplantation (AHCT) or RVD (lenalidomide, bortezomib, dexamethasone) consolidation as post-AHCT interventions did not improve outcomes vs single transplantation and lenalidomide maintenance in transplantation-eligible multiple myeloma.
As noted by the investigators, single-cycle melphalan at 200 mg/m2 and AHCT followed by lenalidomide maintenance has improved progression-free and overall survival in transplantation-eligible patients. The current trial was undertaken to evaluate additional interventions in this setting.
Study Details
In the trial, patients from 54 transplantation centers with symptomatic multiple myeloma within 12 months from starting therapy and without progression who were aged ≤ 70 years were randomly assigned 1:1:1 between June 2010 and November 2013 to receive tandem AHCT/AHCT plus lenalidomide maintenance (n = 247), AHCT plus RVD and lenalidomide maintenance (n = 254), or AHCT plus lenalidomide maintenance (n = 257). All patients were to receive high-dose melphalan (200 mg/m2) followed by mobilized autologous peripheral blood stem-cell infusion.
The primary endpoint was 38-month progression-free survival.
Treatment Outcomes
Progression-free survival at 38 months was 58.5% in the AHCT/AHCT plus lenalidomide group, 57.8% in the AHCT plus RVD plus lenalidomide group, and 53.9% in the AHCT plus lenalidomide group. Overall survival at 38 months was 81.8% for AHCT/AHCT plus lenalidomide, 85.4% for AHCT plus RVD plus lenalidomide, and 83.7% for AHCT plus lenalidomide. Cox proportional hazards models exploring the association between progression-free survival and risk strata and treatment group showed no significant effect for treatment group (P = .48); similar results were observed for models for overall survival (P = .52).
Complete response rates at 1 year were 50.5%, 58.4%, and 47.1% in the 3 groups. Toxicity profiles and development of second primary malignancies were similar among treatment groups.
The investigators concluded, “Second AHCT or RVD consolidation as post-AHCT interventions for the upfront treatment of transplantation-eligible patients with multiple myeloma did not improve [progression-free survival] or [overall survival]. Single AHCT and [lenalidomide] should remain as the standard approach for this population.”
Edward A. Stadtmauer, MD, of the Perelman Center for Advanced Medicine, University of Pennsylvania, is the corresponding author for the Journal of Clinical Oncology article.
Disclosures: The study was supported by a grant from the National Heart, Lung, and Blood Institute and the National Cancer Institute, Celgene Corporation and Millennium (Takeda) Pharmaceuticals, and The Alliance for Clinical Trials in Oncology, the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group, and Southwest Oncology Group (SWOG). The study authors' full disclosures can be found at jco.ascopubs.org.
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®.
