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塞利尼索:一种首创的核输出抑制剂,用于多发性骨髓瘤的多次复发治疗。

Selinexor: A First-in-Class Nuclear Export Inhibitor for Management of Multiply Relapsed Multiple Myeloma.

机构信息

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

出版信息

Ann Pharmacother. 2020 Jun;54(6):577-582. doi: 10.1177/1060028019892643. Epub 2019 Dec 2.

Abstract

To review the pharmacology, pharmacokinetics, efficacy, and safety of selinexor for management of relapsed multiple myeloma (MM). A literature search was performed of PubMed and MEDLINE databases (January 1, 2000, to November 14, 2019), abstracts from the American Society of Hematology and the American Society of Clinical Oncology, and ongoing studies from US National Institutes of Health ClinicalTrials.gov. Queries were performed using key words , and Human and animal studies related to the pharmacology, pharmacokinetics, efficacy, and safety of selinexor were identified. Although numerous advances have been made in MM management, there remains an unmet need for treatment of heavily relapsed/refractory disease. Selinexor is a first-in-class selective inhibitor of nuclear export, which, through inhibition of exportin-1, causes accumulation of tumor suppressor proteins, reduction in oncoproteins, and apoptosis of plasma cells. Selinexor exhibited an overall response in 26% of patients with multiply relapsed MM. Median progression-free survival was 3.7 months, and overall survival was 8.6 months. Common adverse effects include thrombocytopenia, neutropenia, fatigue, and nausea. Ongoing studies are investigating combination therapies utilizing selinexor. This review describes the efficacy, safety, and clinical applicability of selinexor, a novel agent with potential to meet an unmet need in refractory MM. Selinexor has demonstrated activity in a heavily refractory patient population. Given the adverse effect profile and associated costs, additional studies are needed to further elucidate the appropriate clinical scenario and combinations for selinexor use.

摘要

回顾塞利尼索治疗复发性多发性骨髓瘤(MM)的药理学、药代动力学、疗效和安全性。对 PubMed 和 MEDLINE 数据库(2000 年 1 月 1 日至 2019 年 11 月 14 日)、美国血液学会和美国临床肿瘤学会的摘要以及美国国立卫生研究院 ClinicalTrials.gov 的正在进行的研究进行了文献检索。使用关键词进行了查询,确定了与塞利尼索的药理学、药代动力学、疗效和安全性相关的人类和动物研究。尽管在 MM 治疗方面取得了许多进展,但对于复发性/难治性疾病的治疗仍存在未满足的需求。塞利尼索是一种首创的核输出抑制剂,通过抑制输出蛋白 1,导致肿瘤抑制蛋白积累、致癌蛋白减少和浆细胞瘤凋亡。塞利尼索在多发性复发性 MM 患者中的总体反应率为 26%。无进展生存期中位数为 3.7 个月,总生存期为 8.6 个月。常见的不良反应包括血小板减少症、中性粒细胞减少症、疲劳和恶心。正在进行的研究正在调查利用塞利尼索的联合治疗。本综述描述了塞利尼索的疗效、安全性和临床适用性,这是一种具有潜在能力满足难治性 MM 未满足需求的新型药物。塞利尼索在难治性患者群体中显示出活性。鉴于不良反应谱和相关成本,需要进一步研究以进一步阐明塞利尼索使用的适当临床情况和联合用药。

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本文引用的文献

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