This single‑arm, open‑label, prospective observational study evaluated the efficacy and safety of adding oral selinexor to a bortezomib, lenalidomide, and dexamethasone backbone (the XVRd regimen) in patients with newly diagnosed multiple myeloma (NDMM) who presented with high‑risk features. The trial specifically targeted an unmet need in patients with extramedullary disease (EMD), plasma cell leukemia (PCL), and/or adverse cytogenetic abnormalities, aiming to assess response rates, minimal residual disease (MRD) status, and survival outcomes.
Patients were recruited between August 2022 and November 2024 in a multi‑center setting. The protocol comprised an induction phase delivered in 21‑day cycles and a maintenance phase delivered in 28‑day cycles. During induction, enrolled patients aged 18 years or older received the XVRd regimen that included oral selinexor 60 mg administered weekly in combination with bortezomib, lenalidomide, and dexamethasone. After completing induction, patients transitioned to maintenance therapy consisting of selinexor plus lenalidomide.
A total of 30 patients were enrolled. The median age was 62.1 years, with a range from 47 to 73 years. Notably, 24 patients (80%) presented with extramedullary plasmacytoma or plasma cell leukemia, reflecting a cohort enriched for high‑risk clinical features. Additional baseline details such as the distribution of cytogenetic abnormalities or performance status were not provided in the abstract.
The prespecified primary endpoints were the overall response rate (ORR) and the rate of MRD negativity following induction treatment. Secondary endpoints included progression‑free survival (PFS), safety, and tolerability assessments. The abstract reports response categories according to standard myeloma response criteria (sCR, CR, VGPR, PR) and provides survival estimates; granular safety data beyond an overall characterization were not detailed in the abstract.
Across the entire study cohort, the ORR was 93.3% (28 of 30 patients). Response depth included 5 patients achieving stringent complete response (sCR), 9 achieving complete response (CR), 4 achieving very good partial response (VGPR), and 10 achieving partial response (PR). These findings indicate a high overall activity of the XVRd regimen in this predominantly high‑risk NDMM population.
After induction treatment, 5 patients (16.7%) achieved MRD negativity. The abstract does not report the method, sensitivity threshold, or timing used for MRD assessment; those details were not reported in the available source text.
Median progression‑free survival (PFS) for the cohort was reported as 16.2 months (95% CI, 14.6–NA). The 1‑year PFS rate was 89% (95% CI, 0.78–1). Median overall survival (OS) had not been reached at the time of reporting. The abstract provides these survival estimates but does not detail follow‑up duration or censoring specifics beyond the reported confidence intervals.
The overall safety profile was described as manageable. The plain language summary notes that most adverse events were grade 1–2; however, the abstract does not enumerate specific adverse events, their frequencies, or rates of dose modification, discontinuation, or grade ≥3 toxicity. Therefore, detailed safety and tolerability data were not reported in the source abstract.
The authors summarize that the XVRd regimen (selinexor combined with VRd) produces promising efficacy in newly diagnosed, high‑risk multiple myeloma, achieving a high overall response rate of 93.3%, a median PFS of 16.2 months, and a 1‑year PFS rate of 89%. The safety profile was characterized as manageable with most adverse events grade 1–2 according to the plain language summary.
The investigators conclude that the XVRd regimen may yield promising efficacy with a tolerable safety profile for NDMM patients with extramedullary disease and/or high‑risk cytogenetic abnormalities. The study is registered in the Chinese Clinical Trial Registry under registration number ChiCTR2200062860. Specific details on cytogenetic subgroups, MRD assay methodology, comprehensive safety data, and long‑term follow‑up were not reported in the abstract and would require consultation of the full article for complete results and methodology.