Quadruplet regimens for patients with newly diagnosed multiple myeloma: A systematic review and meta-analysis

Quadruplet regimens (anti-CD38 monoclonal antibodies (mAbs) with proteosome inhibitor (PI) and immunomodulatory (IMID) drugs) are increasingly being investigated in newly diagnosed multiple myeloma (NDMM). The objective of our study was to conduct a systematic review and meta-analysis to measure the efficacy and toxicity of quadruplet regimens utilized in NDMM. Embase, Medline, Web of Science, Cochrane Library, clinical trial registries, and meeting libraries from inception to January 24, 2024, in addition to ASCO conference abstracts 2024 were searched using terms reflecting MM and component of the quadruplet regimen. Included studies were randomized controlled trials (RCTs) that compared backbone regimens consisting of a PI and IMID versus the same regimen plus an anti-CD38 mAb in NDMM. We identified seven RCTs including 3716 patients. Compared to triplets, quadruplets increase the overall response rate (ORR, relative risk [RR] 1.03, 95% confidence interval [CI] 1.01-1.05), and progression free survival (PFS, hazard ratio [HR]] 0.55, 95% CI 0.46-0.66). Quadruplets increase the rates of minimal residual disease (MRD) negativity at 10-5 (RR 1.39, 95% 1.23-1.58) and at 10-6 (RR 1.62, 95% CI 1.36-1.94). Quadruplets improve overall survival (OS, HR 0.65, 95% CI 0.53-0.79). There was a slight increase in the rates of grade 3-4 infections (RR 1.22 [95% CI 1.07-1.39]) noted with quadruplets compared to triplets. Overall, in this meta-analysis quadruplets were associated with improved efficacy including ORR, MRD negativity, PFS and OS with a slight increase in infection rates. Quadruplet regimens represent a new standard of care particularly in transplant eligible NDMM.