Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA.
Int J Mol Sci. 2020 Jul 22;21(15):5192. doi: 10.3390/ijms21155192.
During the past two decades there has been a major shift in the choice of agents to treat multiple myeloma, whether newly diagnosed or in the relapsed/refractory stage. The introduction of new drug classes, such as proteasome inhibitors, immunomodulators, and anti-CD38 and anti-SLAMF7 monoclonal antibodies, coupled with autologous stem cell transplantation, has approximately doubled the disease's five-year survival rate. However, this positive news is tempered by the realization that these measures are not curative and patients eventually relapse and/or become resistant to the drug's effects. Thus, there is a need to discover newer myeloma-driving molecular markers and develop innovative drugs designed to precisely regulate the actions of such putative targets. B cell maturation antigen (BCMA), which is found almost exclusively on the surfaces of malignant plasma cells to the exclusion of other cell types, including their normal counterparts, has emerged as a specific target of interest in this regard. Immunotherapeutic agents have been at the forefront of research designed to block BCMA activity. These agents encompass monoclonal antibodies, such as the drug conjugate belantamab mafodotin; bispecific T-cell engager strategies exemplified by AMG 420; and chimeric antigen receptor (CAR) T-cell therapeutics that include idecabtagene vicleucel (bb2121) and JNJ-68284528.
在过去的二十年中，多发性骨髓瘤的治疗药物选择发生了重大转变，无论是新诊断的还是复发/难治性的。新的药物类别（如蛋白酶体抑制剂、免疫调节剂、抗 CD38 和抗 SLAMF7 单克隆抗体）的引入，加上自体干细胞移植，使该病的五年生存率提高了近一倍。然而，这一积极的消息也带来了一个认识，即这些治疗方法并不能治愈疾病，患者最终会复发和/或对药物的作用产生耐药性。因此，需要发现新的多发性骨髓瘤驱动分子标志物，并开发旨在精确调节这些潜在靶点作用的创新药物。B 细胞成熟抗原（BCMA）几乎只存在于恶性浆细胞表面，而排除了其他细胞类型，包括其正常对应物，已成为这方面的一个特定的研究靶点。免疫治疗药物一直处于旨在阻断 BCMA 活性的研究前沿。这些药物包括单克隆抗体，如药物偶联物 belantamab mafodotin；双特异性 T 细胞衔接策略，如 AMG 420；以及嵌合抗原受体（CAR）T 细胞疗法，包括 idecabtagene vicleucel（bb2121）和 JNJ-68284528。
