Hanamura Ichiro, Iida Shinsuke
Department of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine.
Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences.
Rinsho Ketsueki. 2018;59(5):529-538. doi: 10.11406/rinketsu.59.529.
Proteasome inhibitors and immunomodulatory drugs have substantially improved the clinical outcomes in patients with multiple myeloma (MM) since 2000. In 2015, the new monoclonal antibodies, daratumumab and elotuzumab, were approved for treating relapsed and/or refractory MM (RRMM). Furthermore, venetoclax, a selective BCL-2 inhibitor, and chimeric antigen receptor (CAR) T-cell therapy that work against B-cell maturation antigen (BCMA) have reportedly shown great efficacy in phase 1 studies. The efficacy of venetoclax has been observed in RRMM with t (11;14) and higher BCL-2/BCL-X expression. BCMA CAR-T therapies have caused considerable remissions in highly refractory MM. These suggest that personalized medicine and therapy aiming at cure are becoming reality in the near future. MM is a genetically complex and heterogeneous disease that develops via a multistep transformation process. Recent next-generation sequencing (NGS) studies have revealed the molecular landscape, providing insights into the biology, including the intraclonal heterogeneity and disease progression in MM. In this review, we discuss the current knowledge regarding MM genomics reported by NGS studies as well as the recent progress in MM therapy. The agents and treatment reviewed here include elotuzumab, daratumumab, ixazomib, venetoclax, and BCMA CAR-T therapies.
自2000年以来，蛋白酶体抑制剂和免疫调节药物已显著改善了多发性骨髓瘤（MM）患者的临床结局。2015年，新型单克隆抗体达雷妥尤单抗和埃罗妥珠单抗被批准用于治疗复发和/或难治性MM（RRMM）。此外，选择性BCL-2抑制剂维奈克拉以及针对B细胞成熟抗原（BCMA）的嵌合抗原受体（CAR）T细胞疗法在1期研究中据报道已显示出巨大疗效。在伴有t（11；14）以及更高BCL-2/BCL-X表达的RRMM中已观察到维奈克拉的疗效。BCMA CAR-T疗法已在高度难治性MM中引起了相当程度的缓解。这些表明针对治愈的个性化医学和疗法在不久的将来正成为现实。MM是一种通过多步骤转化过程发展而来的基因复杂且异质性的疾病。最近的下一代测序（NGS）研究揭示了分子格局，为MM的生物学特性提供了见解，包括克隆内异质性和疾病进展。在本综述中，我们讨论了NGS研究报告的关于MM基因组学的当前知识以及MM治疗的最新进展。此处所综述的药物和治疗包括埃罗妥珠单抗、达雷妥尤单抗、伊沙佐米、维奈克拉以及BCMA CAR-T疗法。
