A novel conditioning regimen combining selinexor with melphalan  Improves Survival in Patients with multiple myeloma:a prospective study

作者：Liangliang Ma, Jingping Zhang, Xiaoqing Chen, Shanglun Yang, Youmei Fei, Qian Hu, Lejia Liu, Ruting Liao, Jian Li, Caigang Xu, Ting Niu, Yongqian Jia · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-5837 · 研究领域：Nuclear Structure and Function、Multiple Myeloma Research and Treatments、Cell death mechanisms and regulation

Abstract Background: High-dose melphalan followed by autologous hematopoietic stem cell transplantation (ASCT) remains the standard consolidation therapy for multiple myeloma (MM). Previous attempts to optimize conditioning regimens have not yielded superior outcomes. Selinexor, a selective inhibitor of exportin-1 (XPO-1), has demonstrated synergistic antitumor effects with melphalan in preclinical models. Aims: To evaluate the efficacy and safety of a selinexor-melphalan conditioning regimen. Methods: Based on the recommended phase 2 dose (RP2D) established by Nishihori et al., the initial regimen administered selinexor 60 mg on days -4 and -1 combined with melphalan 100 mg/m² on days -3 and -2. Due to severe vomiting (leading to Mallory-Weiss syndrome) in the first patient, the protocol was amended to selinexor 60 mg on days -11 and -4 and melphalan 100 mg/m² (70 mg/m² for creatinine clearance <60 mL/min) on days -3 and -2. The study was approved by the institutional ethics committee, with written informed consent obtained from all participants. Results: From January 2022 to May 2025, 32 MM patients (median age 59 years, range 33-69; male:female 16:16) achieving ≥partial response(PR) post-induction were enrolled. Baseline characteristics included renal dysfunction (CrCl <60 mL/min, n=5), immunoglobulin subtypes (IgG=16, IgA=9, IgD=2, light chain=5) and high-risk features:R-ISS stage III(n=7, 22%),del(17p)(n=1, 3%),TP53 mutation(n=1, 3%), t(4;14)(n=1, 3%)and 1q...