Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Department of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Expert Rev Hematol. 2021 Aug;14(8):697-706. doi: 10.1080/17474086.2021.1923473. Epub 2021 Jul 21.
Multiple myeloma (MM) is an increasingly treatable but still incurable hematologic malignancy. Prognosis has improved significantly over recent years, although further advances remain urgently needed, especially for patients with heavily pre-treated and resistant disease for whom there are limited options. Selinexor is a first-in-class, oral, selective inhibitor of nuclear export (SINE) compound that triggers apoptosis in malignant cells by inducing nuclear retention of oncogene messenger RNAs (mRNAs) and reactivation of tumor suppressor proteins (TSPs). In clinical studies of patients with relapsed and/or refractory MM, selinexor has demonstrated both manageable toxicity and encouraging efficacy.
This review will provide an overview of the mechanism of action of selinexor as well as the efficacy and safety data from clinical studies using selinexor for the treatment of multiple myeloma.
Long-term outcomes for patients with MM will continue to improve due to numerous recent and imminent therapeutic advances, although critical areas of unmet need remain. Oral selinexor is likely to contribute to the meeting of these needs and the further advancement of MM therapy in a meaningful way.
多发性骨髓瘤（MM）是一种日益可治疗但仍无法治愈的血液恶性肿瘤。近年来，其预后有了显著改善，但仍迫切需要进一步的进展，特别是对于那些接受过多重预处理且耐药的患者，他们的选择有限。Selinexor 是一种首创的、口服的、选择性核输出抑制剂（SINE）化合物，通过诱导致癌基因信使 RNA（mRNA）的核内滞留和肿瘤抑制蛋白（TSP）的重新激活，在恶性细胞中引发细胞凋亡。在复发和/或难治性 MM 患者的临床研究中，selinexor 表现出可管理的毒性和令人鼓舞的疗效。
本综述将概述 selinexor 的作用机制，以及临床研究中使用 selinexor 治疗多发性骨髓瘤的疗效和安全性数据。
由于最近和即将出现的许多治疗进展，MM 患者的长期预后将继续改善，但仍存在关键的未满足需求领域。口服 selinexor 很可能会以有意义的方式满足这些需求，并进一步推进 MM 的治疗。
