Background: In the management of transplant-ineligible multiple myeloma (MM), therapeutic strategies are crucial for improving patient outcomes. Recent clinical trials have explored the efficacy of triplet vs dual therapy in this context. This meta-analysis aimed to evaluate the comparative effectiveness (overall survival [OS], progression-free survival [PFS], minimal residual disease [MRD] negative, and response rate [RR]) of Triplet vs Dual therapy in transplant-in-eligible multiple myeloma.
Methods: This meta-analysis of Phase 3 clinical trials aimed to evaluate overall survival (OS), progression-free survival (PFS), mortality, minimal residual disease (MRD) negativity, and response rate (RR) in triplet versus dual therapy for transplant-ineligible multiple myeloma patients. The PRISMA protocol guided the search strategy, using targeted keywords to identify relevant clinical trials from the past 10 years across databases. Non-clinical trials, non-human, non-English, and non-full-text studies were excluded. Abstracts were screened using eligibility criteria, and full-text articles were further evaluated for inclusion in the meta-analysis. Data on study design, population characteristics, intervention type, and outcomes were extracted. Statistical analysis was performed using Review Manager 5.3 software, employing random-effects models to calculate pooled odds ratios with 95% confidence intervals (CIs), with forest plots generated to illustrate findings. Heterogeneity (I²) was assessed, and p-values < 0.05 were considered statistically significant. The Newcastle-Ottawa Scale (NOS) was used to evaluate the risk of bias in included studies.
Results: Out of 51 studies, fulfilling the criteria, three studies had data on the management of TIMM. We found 660 patients in Triple therapy and 717 patients on dual therapy. Triple therapy had higher odds of MRD negative [OR: 2.74, 95%CI: 1.21-6.23, p=0.02, I²: 77%] and RR [2.68, 2.16-3.32, p< 0.00001, I²: 0%] in compared to dual therapy. Triple therapy had 43% lower odds of mortality [Sensitivity analysis: 0.57, 0.42-0.76, p=0.0002, I2: 0%, Crude analysis: 0.74, 0.42-1.28, p=0.28, I²: 63%]. There was no significant difference in OS [0.75, 0.53-1.06, p=0.14, I²: 55%] and PFS [0.87, 0.41-1.88, p=0.73, I²: 92%]. NOS suggested a moderate risk of bias.
Conclusions: In summary, our meta-analysis indicates that triple therapy is superior to dual therapy in patients with multiple myeloma who are ineligible for transplantation. The triple regimen increases the probability of attaining minimal residual disease negativity and improves the response rate. The findings highlight the potential advantages of incorporating an additional medication into treatment protocols to enhance clinical outcomes.
