Objective To analyze the efficacy and safety of the sequential therapy with bortezomib-based triplet regimens excluding lenalidomide followed by continuous lenalidomide and dexamethasone (Rd) in newly diagnosed multiple myeloma (NDMM). Methods Forty NDMM patients were included in this study who were admitted to our center from 2017 to 2019. Bortezomib-based triplet regimens were initially selected and followed by Rd continuous treatment once partial remission (PR) or better was achieved. Efficacy and safety were observed and compared. Results The overall survival rate was 87.5% (35/40), and progression-free survival (PFS) was 50% (20/40) after administration of the sequential strategy. Best outcome assessment achieved during follow-up: 45.0% (18/40) achieved complete response (CR), and 30.0% (12/40) achieved very good partial response (VGPR). 30.0% (12/40) had grade 3-4 or higher drug-related adverse reactions, mainly hematological toxicity, accounting for 25% (10/40). No patients died of adverse reactions. Compared with EVOLUTION trial, this study had more advanced disease stage (ISS stage ⅲ 40.0% vs 19.0%, P=0.037), worse physical status (KPS score 50-60 25.0% vs 2.0%, P=0.003). But there was a higher proportion of ORR (100% vs 73%, P<0.001), VGPR or better (75% vs 32%, P<0.001), and PFS at 12 months (90% vs 68%, P=0.011).Conclusion Bortezomib-based PXD regimens sequential with lenalidomide continuous treatment maybe not be inferior to VRD for first-line treatment in NDMM patients.