Optimal timing and drug combination of selinexor in multiple myeloma: a systematic review and meta-analysis

Multiple myeloma (MM) remains an incurable disease despite advances in treatment options. Recently, selinexor has shown promising efficacy for relapsed/refractory multiple myeloma (RRMM), whereas its optimal timing and drug combination remain unclear. In order to assess the various regimens that incorporate selinexor, a systematic review and meta-analysis was conducted. Clinical trials and real-world studies involving MM patients treated with selinexor were included. Pooled risk ratio (RR) was calculated to compare the rates, along with a 95% confidence interval (CI) and concurrent p-value assessment. A random-effects model was employed to provide a more conservative evaluation. A total of 16 studies enrolling 817 patients were reviewed. The usage of selinexor as the fifth-line or prior therapy achieved a higher objective response rate (ORR) (65.9% versus 23.4%, p p p = 0.26), compared with post-fifth-line usage. Selinexor and dexamethasone (Xd) plus either protease inhibitors (PIs) or immunomodulatory drugs (IMiDs) achieved better ORRs than the Xd-only regimen for RRMM, with ORRs of 56.1%, 52.5% and 24.6%, respectively (p In conclusion, using selinexor as the fifth-line or prior therapy had a beneficial impact on RRMM. The regimen of Xd plus PIs or IMiDs was recommended.尽管治疗手段不断进步，多发性骨髓瘤（Multiple myeloma, MM）仍属不治之症。近年来，塞利尼索（selinexor）在复发难治性多发性骨髓瘤（relapsed/refractory multiple myeloma, RRMM）中展现出了颇具前景的疗效，但其最佳使用时机与联合用药方案仍不明确。为评估各类含塞利尼索的治疗方案，本研究开展了一项系统评价与荟萃分析。研究纳入了所有涉及塞利尼索治疗MM患者的临床试验与真实世界研究。通过计算合并风险比（pooled risk ratio, RR）及其95%置信区间（95% confidence interval, CI），并同步开展p值检验以比较各项疗效指标的发生率。本研究采用随机效应模型以提供更为保守的评估结果。最终共纳入16项研究，共计817例患者。分析结果显示，与五线后使用塞利尼索的方案相比，将其作为五线及更早线治疗时，客观缓解率（objective response rate, ORR）更高（65.9% vs 23.4%，p p p = 0.26）。针对RRMM患者，塞利尼索联合地塞米松（Xd）方案分别联合蛋白酶体抑制剂（protease inhibitors, PIs）或免疫调节药物（immunomodulatory drugs, IMiDs）时，其ORR均优于单纯Xd方案，三者ORR分别为56.1%、52.5%与24.6%（p。综上，将塞利尼索作为五线及更早线治疗对RRMM患者具有积极疗效，推荐采用Xd联合PIs或IMiDs的治疗方案。