a Division of Hematologic Malignancy, Jerome Lipper Multiple Myeloma Center , Dana-Farber Cancer Institute , Boston , MA , USA.
b Department of Hematology , VU University Medical Center, Cancer Center Amsterdam , Amsterdam , The Netherlands.
Expert Opin Pharmacother. 2018 Dec;19(17):1949-1968. doi: 10.1080/14656566.2018.1528229. Epub 2018 Nov 13.
Proteasome inhibitors (PIs) are among the backbones of multiple myeloma (MM) treatment; however, their long-term use can be limited by parenteral administration and treatment-related toxicities. Ixazomib, the first oral PI to enter the clinic, is approved around the world, in combination with lenalidomide and dexamethasone, for the treatment of patients with MM who have received at least one prior therapy. Areas covered: This review summarizes the clinical data leading to approval of ixazomib; its pharmacology, efficacy, and safety. Building on the data in relapsed/refractory MM (RRMM), it also reviews the available clinical trial data for ixazomib across the MM treatment algorithm in newly diagnosed MM, RRMM, and as maintenance therapy, and looks ahead to ongoing clinical trials and the expanding role of ixazomib in these indications. Expert opinion: Ixazomib is an efficacious and well-tolerated addition to the treatment armamentarium for RRMM, with benefit as a long-term, continuous therapy for all patients, including 'poor prognosis' patients, such as those with advanced stage disease, high-risk cytogenetic abnormalities, and elderly and frail patients. Data from ongoing clinical studies are expected to expand the role of ixazomib across the MM treatment algorithm and in a broader range of combination regimens.
蛋白酶体抑制剂 (PIs) 是多发性骨髓瘤 (MM) 治疗的骨干药物之一;然而,由于其需要进行肠外给药,且存在治疗相关毒性,因此其长期应用可能会受到限制。伊沙佐米是首个进入临床的口服 PI,已在全球范围内获得批准,与来那度胺和地塞米松联合用于治疗至少接受过一次先前治疗的 MM 患者。
本综述总结了导致伊沙佐米获批的临床数据;其药理学、疗效和安全性。在 RRMM 中的数据基础上,还回顾了伊沙佐米在新诊断 MM、RRMM 以及维持治疗中的整个 MM 治疗方案中的现有临床试验数据,并展望了正在进行的临床试验以及伊沙佐米在这些适应证中的扩展作用。
伊沙佐米是 RRMM 治疗武器库中一种有效且耐受性良好的药物,可作为所有患者的长期连续治疗药物,包括“预后不良”的患者,如晚期疾病、高风险细胞遗传学异常以及老年和体弱患者。预计来自正在进行的临床研究的数据将扩大伊沙佐米在整个 MM 治疗方案以及更广泛的联合治疗方案中的作用。