Ray Upasana, Orlowski Robert Z
Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030-4009, USA.
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 429, Houston, TX 77030-4009, USA.
Pharmaceuticals (Basel). 2023 Apr 14;16(4):590. doi: 10.3390/ph16040590.
Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved in the advanced setting. Most recently, the bispecific anti-BCMA and T-cell-engaging antibody teclistamab has become available, again for patients with relapsed/refractory disease. Another format into which antibodies can be converted to exert anti-tumor efficacy is as antibody-drug conjugates (ADCs), and belantamab mafodotin, which also targets BCMA, represented the first such agent that gained a foothold in myeloma. Negative results from a recent Phase III study have prompted the initiation of a process for withdrawal of its marketing authorization. However, belantamab remains a drug with some promise, and many other ADCs targeting either BCMA or other plasma cell surface markers are in development and showing potential. This contribution will provide an overview of some of the current data supporting the possibility that ADCs will remain a part of our chemotherapeutic armamentarium against myeloma moving forward, and also highlight areas for future development.
多发性骨髓瘤是一种分泌免疫球蛋白的浆细胞恶性肿瘤,目前在新诊断、复发和/或难治性患者中,常使用靶向谱系特异性标志物的单克隆抗体进行治疗,这些抗体可单独使用,也可用于合理设计的联合治疗方案。其中包括抗CD38抗体达雷妥尤单抗和isatuximab,以及抗信号淋巴细胞激活分子家族成员7抗体elotuzumab,它们均以未偶联的形式使用。抗体的单链可变片段也是靶向B细胞成熟抗原(BCMA)的嵌合抗原受体(CAR)的关键组成部分,在CAR T细胞产品idecabtagene vicleucel和ciltacabtagene autoleucel中,这些产品已在晚期患者中获批。最近,双特异性抗BCMA和T细胞衔接抗体teclistamab也已上市,同样用于复发/难治性疾病患者。抗体发挥抗肿瘤疗效的另一种形式是抗体药物偶联物(ADC),靶向BCMA的贝利司他单抗代表了首个在骨髓瘤领域站稳脚跟的此类药物。最近一项III期研究的阴性结果促使启动了撤回其上市许可的程序。然而,贝利司他单抗仍是一种有一定前景的药物,许多其他靶向BCMA或其他浆细胞表面标志物的ADC正在研发中,并显示出潜力。本文将概述一些当前数据,以支持ADC有望继续作为我们对抗骨髓瘤的化疗武器库的一部分,并突出未来的发展方向。