Abstract
BACKGROUND: Triplet regimens, such as bortezomib-lenalidomide-dexamethasone (VRd) and bortezomib-melphalan-prednisone (VMP), were standard treatments for newly diagnosed multiple myeloma (NDMM), but they were non-curative for most patients. The incorporation of daratumumab into these regimens, resulting in quadruplet therapies, has shown improved outcomes, though concerns over increased toxicity remain. METHODS: In this systematic review and meta-analysis, we aimed to compare the efficacy and safety of daratumumab-incorporated quadruplet regimens versus traditional triplet regimens in NDMM. A search of PubMed, EMBASE, and the Cochrane Library identified six randomized controlled trials (RCTs) with 3,056 patients. Outcomes included response rates, minimal residual disease (MRD) negativity rate, progression-free survival (PFS), and adverse events. RESULTS: Compared with triplet regimens, daratumumab-incorporated quadruplet combinations achieved a higher overall survival rate (ORR) (pooled OR = 2.36, 95% CI: 1.56-3.56, P < 0.0001), rate of complete response (CR) or better (pooled OR = 2.35, 95% CI: 1.99-2.77, P < 0.0001), very good partial response (VGPR) or better (pooled OR = 2.58, 95% CI: 1.76-3.79, P < 0.0001) and MRD negativity (pooled OR = 3.55, 95% CI: 2.54-4.96, P < 0.0001). The addition of daratumumab to triplet regimens significantly improved PFS compared with triplet regimens (pooled HR = 0.45, 95% CI: 0.39-0.52, P < 0.0001). Regarding safety, quadruplet regimens were associated with a higher incidence of lymphopenia, upper respiratory tract infection, pyrexia, and pneumonia. CONCLUSION: Incorporating daratumumab into backbone triplet regimens is associated with improved response rates, deeper remission and prolonged PFS with acceptable toxicity profile in patients with NDMM. SYSTEMATIC REVIEW REGISTRATION: https://inplasy.com/inplasy-2024-12-0026/, identifier INPLASY2024120026.