Double vs. single autologous stem cell transplantation in patients with multiple myeloma and high-risk factors: A systematic review and meta-analysis.

Multiple myeloma (MM) remains a challenging hematological malignancy despite therapeutic advances. The present systematic review and meta-analysis aimed to evaluate the comparative efficacy of double vs. single high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) for MM, with a specific interest in its application for individuals presenting with high-risk disease factors. A comprehensive search of the literature available in the PubMed, Cochrane and Embase databases was performed from inception to April 12, 2023. The analysis incorporated randomized controlled trials (RCTs) that directly compared single HDT followed by ASCT (HDT/ASCT; administered with or without consolidation therapy) against double transplantation. A total of 8 RCTs were included in the final meta-analysis. The aggregated data demonstrated a hazard ratio of 0.58 [95% confidence interval (CI), 0.43-0.80; P=0.001] for PFS and 0.70 (95% CI, 0.54-0.90; P=0.006) for overall survival (OS). These results imply that the double HDT/ASCT strategy may confer significant improvements in both PFS and OS for patients with at least one unfavorable prognostic marker. Findings from the network meta-analysis revealed no statistically significant disparities in PFS or OS outcomes when comparing double HDT/ASCT with single HDT/ASCT supplemented with consolidation therapy. Nevertheless, the double transplantation approach was associated with a markedly higher incidence of achieving at least a very good partial response relative to single HDT/ASCT (relative risk, 1.17; 95% CI, 1.03-1.33; P=0.02). Moreover, the risk of treatment-related mortality (TRM) was comparable between the double and single HDT/ASCT cohorts. In conclusion, the results of the present meta-analysis indicate that double HDT/ASCT was associated with a significantly higher rate of achieving at least a very good partial response without elevating TRM in the general MM population, indicating an improved treatment response. Notably, it offers superior PFS and OS advantages for high-risk patients. Therefore, double HDT/ASCT may be regarded as a viable and beneficial therapeutic option for this high-risk subgroup.