Abstract

Introduction

B-cell maturation antigen (BCMA) targeted therapy (BCMA-TT) has emerged as a promising treatment for Multiple Myeloma (MM). the three most common treatment modalities for targeting BCMA are antibody-drug conjugates (ADCs), bispecific antibody constructs, including BiTE (bispecific T-cell engager) immuno-oncology therapies, and chimeric antigen receptor (CAR)-modified T-cell therapy.

Areas covered

: The review provides an overview of the main published studies on clinical and pre-clinical data from trials using BCMA-TT.

Expert opinion

Despite progresses in survival outcomes and the availability of new drugs, MM remains an incurable disease. ADC is a promising antibody-based treatment and Belantamab mafodotin showed an anti-myeloma effect alone or in combination with other drugs. The major issue of ADC is the occurrence of events interfering with the efficacy and the off-target cytotoxicity. Bispecific antibody constructs are off-the-shelf therapies characterized by a potential rapid availability. The most critical limitation of bispecific antibody constructs is their short half-life necessitating prolonged intravenous infusion. CAR-T cells produced unprecedented results in heavily pretreated RRMM. The most common toxicities include neurologic toxicity and cytokine release syndrome, B-cell aplasia, cytopenias, and hypogammaglobulinemia. Further studies are needed to detect which are the eligible patients who could benefit from one treatment more than another.

中文翻译：

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多发性骨髓瘤B细胞成熟抗原靶向疗法的最新进展

摘要

介绍

B细胞成熟抗原（BCMA）靶向治疗（BCMA-TT）已经成为多发性骨髓瘤（MM）的有前途的治疗方法。靶向BCMA的三种最常见的治疗方式是抗体-药物偶联物（ADC），双特异性抗体构建体，包括BiTE（双特异性T细胞接合剂）免疫肿瘤疗法和嵌合抗原受体（CAR）修饰的T细胞疗法。

覆盖区域

：该综述概述了有关使用BCMA-TT进行的临床和临床前数据发表的主要研究。

专家意见

尽管在生存结果和新药的可获得性方面取得了进展，但是MM仍然是无法治愈的疾病。ADC是一种有前途的基于抗体的治疗方法，贝兰单抗mafodotin单独或与其他药物联合使用均显示出抗骨髓瘤作用。ADC的主要问题是干扰功效和脱靶细胞毒性的事件的发生。双特异性抗体构建体是以潜在的快速可用性为特征的现成疗法。双特异性抗体构建体的最关键限制是半衰期短，需要延长静脉输注。在经过大量预处理的RRMM中，CAR-T细胞产生了前所未有的结果。最常见的毒性包括神经毒性和细胞因子释放综合征，B细胞发育不全，血细胞减少和低血球蛋白血症。