This year’s ASH Annual Meeting on Advances in First-Line Treatment of MM focuses on the long-term follow-up results of bortezomib (Vanco) in first-line treatment of MM, particularly the follow-up update of the VMFF-VT regimen and the value of bortezomib in maintenance and sequential therapy. 1. Long-term follow-up results of the VMpT-VT regimen A GIMEMA multicenter, prospective, randomized clinical trial compared the efficacy of two regimens in newly diagnosed MM over 65 years of age. One group was VMP (bortezomib, melphalan, prednisone) induction and the other group was VMPT (bortezomib, melphalan, prednisone, thalidomide) induction + VT maintenance for 2 years (bortezomib 1.3 mg/m , every 2 weeks and thalidomide 50 mg/d). After enrolling 139 patients, the original induction regimen was changed from bortezomib 1.3 mg/m , twice weekly for 6 weeks, to bortezomib 1.3 mg/m2 , once weekly for 5 weeks, after the 1st to 4th course of the original induction regimen. Preliminary results showed that ORR, PFS and time to next treatment were better in the VMPT.VT group than in the VMP group. This annual meeting of the study updated the follow-up results with a median follow-up of 47.2 months and 5-year OS rates of 59.3% and 45.9% in the VMPT-VT and VMP groups, respectively (HR 0.74, p=0.04). The OS benefit was more pronounced in patients under 75 years of age (5-year OS rate 67.8% versus 49.9%, HR 0.63, P=0.01) and in those who achieved CR with induction therapy (5-year OS rate 81.4% versus 48.2%, FIR 0.38, P: 0.006). There was no significant difference in survival time after relapse and salvage therapy between the two groups (2-year 0S rate 40.7% versus 50.2%, P=0.54). This long-term follow-up result suggests that for MM patients aged 65-75 years, the VMPT-VT regimen resulted in a 37% reduction in the risk of death and should be considered as a new standard of care. A PETHEMA/GEM randomized clinical trial randomized 266 MM patients to 3 maintenance regimens after ASCT, including the TV group (thalidomide 100 mg/d, bortezomib 1-3 mg/m. Days 1, 4, 8, and 11 every 3 months), the T group (thalidomide 100 mg/d), and the T group (thalidomide 100 mg/d). amide 100 mg/d) and the interferon α2 group (3MU, 3 times a week). The CR rate increased by 15% -19% in the 3 groups after maintenance treatment, but the difference between the groups was not statistically significant. At a median follow-up of 34.9 months, PFS was significantly longer in the TV group compared with the other 2 groups (P=0.0009), but the difference in 0s between the 3 groups was not statistically significant. The incidence of peripheral neuropathy (PN) was 12.2% and 10.1% in the TV and T groups, respectively, and no grade 4 PN was present. Although bortezomib added to thalidomide maintenance therapy could prolong PFS, it could not overcome the adverse prognostic effect in MM patients with high-risk cytogenetic abnormalities. 3. sequential treatment strategy To improve the quality of MM induction remission, a three-drug induction regimen containing an immunomodulator or proteasome inhibitor or a combination of two new classes of drugs is usually used for induction therapy. The alternative strategy is to sequentially use two different classes of new drugs for optimal efficacy depending on the efficacy of the initial induction regimen. In the Myeloma XI clinical trial, UK investigators randomized patients with newly diagnosed MM to induction therapy with either CTD (cyclophosphamide, thalidomide, dexamethasone) or CRD (cyclophosphamide, lenalidomide, dexamethasone). Patients with no change in disease (NC) or progressive disease (PD) were then selected for subsequent treatment based on the efficacy obtained after adequate treatment. Patients with no change in disease (NC) or progressive disease (PD) were given a CVD regimen (cyclophosphamide, bortezomib, dexamethasone) for re-induction, patients with MR or PR were randomized to receive a CVD regimen or no further treatment, and patients with VGPR or higher did not receive new induction therapy. All young patients were given high-dose melphalan and ASCT. all patients were then entered into a randomized subgroup for maintenance treatment, with the choice of no maintenance or lenalidomide maintenance or lenalidomide combined with vorinostat maintenance. Patients receiving the CVD regimen may be treated for up to 8 courses for maximum efficacy or treated to intolerable regimens. Preliminary analysis showed that of the 1424 patients currently enrolled, 58% of patients with initial induction therapy for NC/PD who were re-induced with the CVD regimen achieved MR or higher and 31% achieved VGPR or CR. 45% of patients randomized to the CVD regimen who achieved MR or PR with initial induction therapy achieved VGPR or CR. These results suggest a sequential treatment strategy with immunomodulator-based induction therapy to achieve MR or CR. The above results suggest that the quality of remission can be further improved with a sequential treatment strategy in which those who achieved MR or PR with immunomodulator-based induction therapy are re-induced with a bortezomib-based regimen. Encouragingly, VGPR or CR rates were also significantly improved after switching to bortezomib for those who failed initial induction therapy. Based on the efficacy achieved with thalidomide-based induction therapy in the Myeloma IX trial (PD/NC rate of 7.1%, MR/PR rate of 41.8%, and VGPR/CR rate of 37.5%), it is assumed that the rate of achieving VGPR or higher in the Myeloma XI trial increased by approximately 21% to 59%. This suggests that sequential treatment strategies can also achieve high-quality remissions, which provides a useful exploration for individualized treatment.