Tufts Medical Center, Boston, Massachusetts.
Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Clin Adv Hematol Oncol. 2020 Nov;18(11):736-748.
Despite continued and considerable progress following the introduction of proteasome inhibitors and immunomodulatory agents, multiple myeloma (MM) remains an incurable disease, and new therapeutic strategies are urgently needed. Monoclonal antibodies represent a well-established targeted approach to the treatment of MM, with selective killing properties and limited off-target toxicity. Since their approval, the anti-CD38 agent daratumumab, the anti-SLAMF7 agent elotuzumab, and most recently the anti-CD38 agent isatuximab have led to pivotal improvements in the treatment of double-refractory MM; currently, they are on their way to becoming integral parts in the up-front care of patients who have newly diagnosed MM, with daratumumab already approved in this setting. Several other antibody-based strategies are undergoing clinical assessment in MM. Although the investigation of checkpoint inhibitors in MM has been halted, bispecific T-cell engagers and especially antibody-drug conjugates demonstrate encouraging efficacy and manageable toxicity in triple class-refractory MM. The accelerated approval of belantamab mafodotin represents an important milestone in antibody development; its ability to target B-cell maturation antigen (BCMA) in advanced disease is now established. Here, we present an overview of the currently available monoclonal antibody treatments in MM and discuss the clinical value, significant potential, and possible limitations of these immunotherapeutic approaches to driving deeper responses and achieving longer overall survival among patients with a challenging disease.
尽管在引入蛋白酶体抑制剂和免疫调节剂后取得了持续且相当大的进展，但多发性骨髓瘤（MM）仍然是一种无法治愈的疾病，迫切需要新的治疗策略。单克隆抗体是治疗 MM 的一种成熟的靶向方法，具有选择性杀伤特性和有限的脱靶毒性。自批准以来，抗 CD38 单克隆抗体达雷妥尤单抗、抗 SLAMF7 单克隆抗体埃罗妥珠单抗以及最近的抗 CD38 单克隆抗体伊沙妥珠单抗，使双难治性 MM 的治疗取得了重大进展；目前，它们正在成为新诊断为 MM 的患者的一线治疗的一部分，达雷妥尤单抗已在该治疗中获得批准。其他几种基于抗体的策略正在 MM 中进行临床评估。尽管 MM 中的检查点抑制剂研究已经停止，但双特异性 T 细胞衔接子，特别是抗体药物偶联物，在三药难治性 MM 中显示出令人鼓舞的疗效和可管理的毒性。贝兰他单抗mafodotin 的加速批准是抗体开发的一个重要里程碑；其在晚期疾病中靶向 B 细胞成熟抗原（BCMA）的能力现已得到确立。在这里，我们介绍了目前在 MM 中可用的单克隆抗体治疗方法，并讨论了这些免疫治疗方法的临床价值、巨大潜力和可能的局限性，这些方法有望在具有挑战性的疾病患者中实现更深层次的缓解和更长的总生存期。
