Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
UOC Laboratorio Analisi Cliniche, Biomolecolari e Genetica, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Expert Opin Pharmacother. 2024 Mar;25(4):421-434. doi: 10.1080/14656566.2024.2333376. Epub 2024 Mar 25.
Selinexor, an XPO1 inhibitor, has emerged as a promising therapeutic option in the challenging landscape of relapsed/refractory multiple myeloma (RRMM).
This article provides a review of selinexor, with a focus on available clinical studies involving MM patients and its safety profile. Clinical trials, such as STORM and BOSTON, have demonstrated its efficacy, particularly in combination regimens, showcasing notable overall response rates (ORR) and prolonged median progressionfree survival (mPFS). Selinexor's versatility is evident across various combinations, including carfilzomibdexamethasone (XKd), lenalidomidedexamethasone (XRd), and pomalidomidedexamethasone (XPd), with efficacy observed even in tripleclass refractory and highrisk patient populations. However, challenges, including resistance mechanisms and adverse events, necessitate careful management. Realworld evidence also underscores selinexor's effectiveness in RRMM, though dose adjustments and supportive measures remain crucial. Ongoing trials are exploring selinexor in diverse combinations and settings, including pomalidomidenaïve patients and postautologous stem cell transplant (ASCT) maintenance.
The evolving landscape of selinexor's role in the sequencing of treatment for RRMM, its potential in highrisk patients, including those with extramedullary disease, as revealed in the most recent international meetings, and ongoing investigations signal a dynamic era in myeloma therapeutics. Selinexor emerges as a pivotal component in multidrug strategies and innovative combinations.
Selinexor 是一种 XPO1 抑制剂,在复发/难治性多发性骨髓瘤(RRMM)这一极具挑战性的治疗领域中展现出了良好的应用前景。
本文综述了 Selinexor,重点介绍了其在 MM 患者中的临床研究结果及其安全性特征。STORM 和 BOSTON 等临床试验表明,Selinexor 具有显著疗效,尤其是在联合治疗方案中,总缓解率(ORR)和中位无进展生存期(mPFS)显著延长。Selinexor 与多种药物联合应用具有广泛的适用性,包括卡非佐米-地塞米松(XKd)、来那度胺-地塞米松(XRd)和泊马度胺-地塞米松(XPd),甚至在三药难治和高危患者群体中也观察到了疗效。然而,包括耐药机制和不良反应在内的诸多挑战需要谨慎管理。真实世界的证据也进一步证实了 Selinexor 在 RRMM 中的有效性,尽管需要调整剂量和采取支持性措施。目前正在进行的临床试验正在探索 Selinexor 在不同联合方案和治疗场景中的应用,包括泊马度胺初治患者和自体造血干细胞移植(ASCT)后的维持治疗。
Selinexor 在 RRMM 治疗序贯治疗中的作用不断演变,在最近的国际会议上揭示了其在高危患者(包括有髓外疾病的患者)中的应用潜力,以及正在进行的研究表明骨髓瘤治疗领域正处于一个充满活力的时代。Selinexor 已成为多药联合策略和创新联合方案中的关键组成部分。