Tamura Hideto
Department of Hematology, Nippon Medical School.
Rinsho Ketsueki. 2018;59(10):2169-2177. doi: 10.11406/rinketsu.59.2169.
Multiple myeloma (MM) involves the immune dysregulation not only of B cells but also of NK, T, and dendritic cells. Furthermore, the number of regulatory T and myeloid-derived immunosuppressive cells, which are associated with disease progression, also increases. Immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide exhibit an antimyeloma effect and improve the immune status. Thus, IMiD-enhanced antibody-dependent cell cytotoxicity increases the cytotoxic activity of monoclonal antibody treatment. Among many antibodies, anti-SLAMF7 elotuzumab and anti-CD38 daratumumab have been approved in Japan, and their targeted antigens are responsible for functions that may influence clinical efficacy. Daratumumab exerts various mechanisms of antitumor activity and enhances T-cell immunity by inhibiting immunosuppressive cells. New monoclonal antibodies, including the anti-CD38 antibody isatuximab and anti-BCMA antibody-drug conjugate, are being developed and are expected to demonstrate clinical efficacy. To improve long-term prognosis and achieve cure for MM, immunotherapies such as IMiD-intensified antibody treatment, which resulted in better response rates and longer survival in refractory/relapsed MM, are essential.
多发性骨髓瘤(MM)不仅涉及B细胞的免疫失调,还涉及自然杀伤细胞、T细胞和树突状细胞的免疫失调。此外,与疾病进展相关的调节性T细胞和髓源性免疫抑制细胞的数量也会增加。来那度胺和泊马度胺等免疫调节药物(IMiDs)具有抗骨髓瘤作用,并能改善免疫状态。因此,IMiD增强的抗体依赖性细胞毒性增加了单克隆抗体治疗的细胞毒性活性。在众多抗体中,抗信号淋巴细胞激活分子家族7(SLAMF7)的埃罗妥珠单抗和抗CD38的达雷妥尤单抗已在日本获批,其靶向抗原具有可能影响临床疗效的功能。达雷妥尤单抗发挥多种抗肿瘤活性机制,并通过抑制免疫抑制细胞增强T细胞免疫。包括抗CD38抗体isatuximab和抗B细胞成熟抗原(BCMA)抗体药物偶联物在内的新型单克隆抗体正在研发中,有望展现临床疗效。为改善MM的长期预后并实现治愈,免疫疗法如IMiD强化抗体治疗至关重要,这种疗法在难治性/复发性MM中产生了更高的缓解率和更长的生存期。