Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy – Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM. FACT-MM data were collected at baseline, on day 1 of each 4-week treatment cycle, and at end of treatment (EOT). Changes from baseline were analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain using mixed-effects regression models. Two approaches for evaluating minimal clinically important differences were explored: the first defined as 10% of the instrument range, and the second based on estimated mean baseline differences between Eastern Cooperative Oncology Group performance status (ECOG PS) scores. Post-hoc difference analysis compared change in scores from baseline to EOT for treatment responders and non-responders. Eighty patients were included in the analysis; the mean number of prior therapies was 7.9 (standard deviation [SD] 3.1), and mean duration of myeloma was 7.6 years (SD 3.4). Each exploratory minimal clinically important difference threshold yielded consistent results whereby most patients did not experience HRQoL decline during the first six cycles of treatment (range: 53.9 to 75.7% for the first approach; range: 52.6 to 72.9% for the second). Treatment responders experienced less decline in HRQoL from baseline to EOT than non-responders, which was significant for the FACT-G, but not for other scores. The majority of patients did not experience decline in HRQoL based on minimal clinically important differences during early cycles of treatment with selinexor and dexamethasone in the STORM trial. An anchor-based approach utilizing patient-level data (ECOG PS score) to define minimal clinically important differences for the FACT-MM gave consistent results with a distribution-based approach. This trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015.

中文翻译：

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多发性骨髓瘤患者的生活质量分析：Selinexor (KPT-330) 难治性骨髓瘤治疗 (STORM) 2b 期研究的结果

Selinexor 是一种口服选择性核输出抑制剂。STORM 是一项 2b 期、单臂、开放标签、多中心试验，在五暴露复发/难治性多发性骨髓瘤 (RRMM) 患者中使用 selinexor 联合低剂量地塞米松，达到了主要终点，总体缓解率为 26% (95 % 置信区间 [CI]，19% 至 35%）。健康相关生活质量 (HRQoL) 是使用癌症治疗功能评估 – 多发性骨髓瘤 (FACT-MM) 测量的次要终点。本研究探讨了 selinexor 治疗对 STORM 治疗患者 HRQoL 的影响，并报告了两种计算 FACT-MM 临床重要差异的方法。FACT-MM 数据在基线、每个 4 周治疗周期的第一天以及治疗结束 (EOT) 时收集。使用混合效应回归模型分析 FACT-MM 总分、FACT-试验结果指数 (TOI)、FACT-General (FACT-G) 和 MM 特定领域相对于基线的变化。探索了两种评估最小临床重要差异的方法：第一种定义为仪器范围的 10%，第二种基于东部肿瘤合作组表现状态 (ECOG PS) 评分之间的估计平均基线差异。事后差异分析比较了治疗有反应者和无反应者从基线到 EOT 的评分变化。分析中纳入了 80 名患者；既往治疗的平均次数为 7.9 次（标准差 [SD] 3.1），骨髓瘤的平均病程为 7.6 年（SD 3.4）。每个探索性最小临床重要差异阈值都产生一致的结果，其中大多数患者在前六个治疗周期中没有经历 HRQoL 下降（范围：第一种方法的 53.9% 至 75.7%；第二种方法的范围：52.6% 至 72.9%）。治疗有反应者的 HRQoL 从基线到 EOT 的下降幅度小于无反应者，这对于 FACT-G 很重要，但对于其他评分则不然。在 STORM 试验中，大多数患者在使用 selinexor 和地塞米松治疗的早期周期中，由于临床上的重要差异极小，因此 HRQoL 并未出现下降。基于锚的方法利用患者水平数据（ECOG PS 评分）来定义 FACT-MM 的最小临床重要差异，与基于分布的方法得到了一致的结果。该试验于 2015 年 1 月 8 日在 ClinicalTrials.gov 上注册，试验 ID 为 NCT02336815。