Multiple Myeloma: Myeloablative Therapy with Autologous Stem Cell Support versus Chemotherapy: A Meta-analysis

Background: Myeloablative high-dose chemotherapy (HDT) followed by single autologous stem cell transplantation is currently the standard treatment for patients younger than 65 years with newly diagnosed multiple myeloma (MM). Several randomized controlled trials (RCTs) comparing HUT with standard dose therapy (SDT) have shown some benefit in overall survival (OS) and progression-free survival (PFS), whereas other RCTs did not confirm this finding. In this study we attempted to analyze the current data in terms of the endpoints OS and PFS. Materials and Methods: We searched PubMed. Embase, abstracts of former ASH meetings and ClinicalTrials.gov, as well as bibliographies of included trials, and recent reviews from September 2009 until May 2010. Amongst the 3,484 results in this search, we identified 10 RCTs comparing HDT with SDT on an intention-to-treat-basis. Treatment characteristics and outcomes of OS and PFS were reported. We investigated statistical heterogenity and publication bias and performed subgroup analyses. Results: Nine RCTs including 2,600 patients were fully analyzed. Patients undergoing HDT with stem cell transplantation had a significant PFS benefit (hazard ratio=0.73; 95% CI=0.56-0.95; p=0.02) but no OS benefit (HR 0.90; 95% CI 0.74-1.10; p=0.32) as compared to patients undergoing SDT. Conclusion: Although there is only a trend of OS benefit with HDT, it is currently still the first line treatment. Additional data from ongoing clinical trials and new studies using novel agents such as thalidomide, lenalidomide and bortezomib are warranted to finally evaluate the role of HDT in the treatment management of patients with newly diagnosed MM.