Objective To evaluate the real-world effectiveness and safety of the in-class transition(iCT)from the protease inhibitors(PI)Bortezomib to Ixazomib for the treatment of patients with newly diagnosed multiple myeloma(NDMM).Methods In this retrospective study,fifty patients with NDMM who had early iCT from Bortezomib to Ixazomib during the induction or consolidation phase were included at Anhui Cancer Hospital from December 2018 to July 2021.The effectiveness and safety of Ixazomib-based treatment were assessed.Results The median treatment cycles was 10.5(1.0-39.0)and 14.5(3.0-45.0)for Ixazomib and PI,respectively.The overall response rate(ORR)improved from 90%(45/50)to 98%(49/50)and the complete response(CR)rate from 46%(23/50)to 72%(36/50)after iCT.With a median follow-up duration of 39.0(6.0-56.0)months,the median progression-free survival(PFS)of 49 months and the median overall survival(OS)was not reached.The 2-year PFS and OS rate was 78%and 94%,respectively.In the subgroup analysis,the 2-year PFS and OS rates after iCT in patients with 1 q21 amplification were 75%and 88.9%,respectively.Patients received Ixazomib for ≥12 cycles had significantly improved OS than those did not(2-year OS 100%vs.89.3%,4-year OS 88.8%vs.52.3%,P=0.0337).The incidence of adverse events(AEs)of any grade was 90%during Ixazomib-based treatment,with predominantly grade 1-2 AEs.Grade 3 AEs occurred in 8%of the patients and no grade 4 AE occurred.The most common non-hematological AEs were peripheral neuropathy(56%)and diarrhea(36%).Conclusion Early iCT from Bortezomib to Ixazomib for NDMM might deepen the response and reduce the risk of adverse events,which might enable the continuous anti-tumor treatment and improve the long-term survival.