The Efficacy and Safety of Tandem Transplant Versus Single Stem Cell Transplant for Multiple Myeloma Patients: A Systematic Review and Meta-Analysis.

Background: While high-dose therapy and autologous stem cell transplant (ASCT) remain integral to the primary treatment of newly diagnosed transplant-eligible multiple myeloma (MM) patients, the challenge of disease progression persists. The primary objective of this meta-analysis is to evaluate the efficacy and safety of tandem ASCT compared to single ASCT. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies comparing tandem ASCT with single ASCT in patients with newly diagnosed MM. We searched PubMed, EMBASE, Cochrane Library, and Clinical Trials databases for studies published up to January 2024. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR), complete response rate (CRR), and treatment-related mortality (TRM). We used a random-effects model to calculate pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Study quality was assessed using the Cochrane Risk of Bias tool and Newcastle-Ottawa Scale. Results: Eleven studies involving 4862 patients met the inclusion criteria. Tandem ASCT was associated with a significantly higher CRR compared to single ASCT (OR 1.34, 95% CI 1.10–1.63, I2 = 31%), but no significant differences were observed in PFS (HR 0.76, 95% CI 0.44–1.33, I2 = 15%), OS (HR 0.63, 95% CI 0.36–1.09, I2 = 28%), or the ORR (OR 0.92, 95% CI 0.75–1.10, I2 = 31%). However, tandem ASCT was associated with a significantly higher risk of TRM (OR 2.36, 95% CI 1.76–3.16, I2 = 31%). Conclusions: Tandem ASCT improves CRR but does not provide significant benefits in terms of PFS, OS, or ORR compared to single ASCT in patients with newly diagnosed MM. Moreover, tandem ASCT is associated with a higher risk of TRM. The decision to pursue tandem ASCT should be made on an individual basis, carefully weighing the potential benefits and risks in light of each patient’s unique clinical situation. Future research should focus on identifying patient subgroups most likely to benefit from tandem ASCT and exploring strategies to optimize the efficacy and safety of this approach in the context of novel agent-based therapies.