Selinexor combined bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma with high-risk factors: a single-arm, multi-center, prospective observational clinical study

OBJECTIVE: This study aimed to evaluate the efficacy and safety of selinexor combined with bortezomib, lenalidomide, and dexamethasone (the XVRd regimen) for newly diagnosed multiple myeloma (NDMM) patients with high-risk features. METHODS: This single-arm, open-label, prospective observational study recruited patients between August 2022 and November 2024. The study consisted of an induction phase (21-day cycles) and a maintenance phase (28-day cycles). During induction, all enrolled patients aged ≥18 years received the XVRd regimen containing oral selinexor 60 mg weekly. After induction, patients transitioned to maintenance therapy with selinexor plus lenalidomide. The primary endpoints were the overall response rate (ORR) and minimal residual disease (MRD) negative rate. Secondary endpoints included progression-free survival (PFS), treatment safety, and tolerability. RESULTS: A total of 30 patients were enrolled, with a median age of 62.1 years (range, 47-73 years). Twenty-four patients (80%) presented with extramedullary plasmacytoma or plasma cell leukemia (PCL). The ORR across the entire cohort was 93.3% (28/30), including 5 patients with stringent complete response (sCR), 9 with complete response (CR), 4 with very good partial response (VGPR), and 10 with partial response (PR). Five patients (16.7%) achieved MRD negativity after induction treatment. Survival analysis demonstrated a median PFS of 16.2 months (95% CI, 14.6-NA), a 1-year PFS rate of 89% (95% CI, 0.78-1), and unreached median overall survival (OS). The overall safety profile was manageable. CONCLUSION: The XVRd regimen may yield promising efficacy with a tolerable safety profile in NDMM patients with extramedullary disease (EMD) and/or high-risk cytogenetic abnormalities. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, registration number: ChiCTR2200062860.