Lowering the Selinexor Dose within the Pomalidomide and Dexamethasone Combination Regimen Elicits Fewer Side Effects While Comparable Efficacy Against Relapsed/Refractory Multiple Myeloma.

IF 2.7 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2025-06-06 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S516486

Liying Peng, Tiantian Shan, Xinyi Zhou, Zhongyuan Feng, Wanting Qiang, Jing Lu, Haiyan He, Juan Du

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引用次数: 0

Abstract

Background: As a novel oral Exportin 1 (XPO1) inhibitor, selinexor at 80 or 100 mg has demonstrated efficacy in treating relapsed/refractory multiple myeloma (RRMM), nonetheless, this dosage has shown poor tolerability.

Objective: To explore the optimal dosage of selinexor, we evaluated the efficacy and safety of 60 vs 40 mg selinexor, combine with regimen comprising pomalidomide and dexamethasone in RRMM.

Design: 21 patients with RRMM were enrolled to receive selinexor (60 or 40 mg once weekly), together with pomalidomide (4 mg/day on days 1-21) and dexamethasone (40 mg once weekly); the SPD-60 group (6 patients) vs SPD-40 group (15 patients).

Methods: The clinical response and efficacy of the two groups were continuously followed up, and statistical analysis was carried out to screen out the dose group with fewer side effects and better efficacy. The primary endpoint was (objective response rates) ORR. The secondary endpoints included treatment safety and tolerability, progression-free survival (PFS) and overall survival (OS).

Results: The ORR of the SPD-60 and SPD-40 groups were 33.3% and 46.7% respectively (P=0.773). With a median follow-up of 20.9 months, the median PFS was 6.2 months and the median OS was not achieved across all treated patients. The median PFS for SPD-60 group was 4.3 months, while for SPD-40 was 8.0 months (P=0.618). The 1-year OS rate were 66.7% for SPD-60 group and 85.1% for the SPD-40 group (P=0.308). The most common hematological adverse events were neutropenia (SPD-60 group 50% vs SPD-40 group 53.3%) and thrombocytopenia (50% vs 46.7%). Fatigue (83.3% vs 40%), infection (50% vs 53.3%), and nausea (83.3% vs 40%) were the most common non-hematologic adverse effects.

Conclusion: The SPD-40 regimen may be more clinically applicable than SPD-60, as it elicited fewer adverse effects while demonstrating equivalent efficacy.

Trial registration: ClinicalTrials.gov: NCT04941937.

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在泊马度胺和地塞米松联合治疗方案中降低塞利那索的剂量可以减少副作用，同时对复发/难治性多发性骨髓瘤的疗效相当。

背景：作为一种新型的口服出口蛋白1 （XPO1）抑制剂，80或100 mg的selinexor治疗复发/难治性多发性骨髓瘤（RRMM）有疗效，但该剂量耐受性较差。目的：探讨selinexor的最佳剂量，评价selinexor 60mg与40mg联合泊马度胺、地塞米松治疗RRMM的疗效和安全性。设计：21例RRMM患者入组接受selinexor（60或40 mg，每周1次）、pomalidomide （4 mg/天，第1-21天）和地塞米松（40 mg，每周1次）；SPD-60组（6例）vs SPD-40组（15例）。方法：对两组患者的临床反应和疗效进行持续随访，并进行统计分析，筛选出副作用少、疗效好的剂量组。主要终点为ORR（客观缓解率）。次要终点包括治疗安全性和耐受性、无进展生存期（PFS）和总生存期（OS）。结果：SPD-60组、SPD-40组的ORR分别为33.3%、46.7% （P=0.773）。中位随访20.9个月，中位PFS为6.2个月，中位OS未达到所有治疗患者。SPD-60组的中位PFS为4.3个月，SPD-40组的中位PFS为8.0个月（P=0.618）。SPD-60组1年OS率为66.7%，SPD-40组为85.1% （P=0.308）。最常见的血液学不良事件是中性粒细胞减少（SPD-60组50% vs SPD-40组53.3%）和血小板减少（50% vs 46.7%）。疲劳（83.3%对40%）、感染（50%对53.3%）和恶心（83.3%对40%）是最常见的非血液学不良反应。结论：SPD-40方案可能比SPD-60方案更具有临床适用性，其不良反应较少，且疗效相当。试验注册：ClinicalTrials.gov: NCT04941937。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.