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多发性骨髓瘤中靶向B细胞成熟抗原疗法的最新进展

An update on B-cell maturation antigen-targeted therapies in Multiple Myeloma.

作者信息

Martino Massimo, Paviglianiti Annalisa

机构信息

Stem Cell Transplant and Cellular Therapies Unit, Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy.

出版信息

Expert Opin Biol Ther. 2021 Aug;21(8):1025-1034. doi: 10.1080/14712598.2021.1872540. Epub 2021 Jan 13.

Abstract

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

摘要

B细胞成熟抗原(BCMA)靶向治疗(BCMA-TT)已成为治疗多发性骨髓瘤(MM)的一种有前景的疗法。靶向BCMA的三种最常见治疗方式是抗体药物偶联物(ADC)、双特异性抗体构建体,包括双特异性T细胞衔接器(BiTE)免疫肿瘤疗法,以及嵌合抗原受体(CAR)修饰的T细胞疗法。

本综述概述了使用BCMA-TT进行试验的临床和临床前数据的主要已发表研究。

尽管在生存结果方面取得了进展,且有新药可供使用,但MM仍然是一种无法治愈的疾病。ADC是一种有前景的基于抗体的治疗方法,贝兰他单抗莫福汀单独或与其他药物联合使用时显示出抗骨髓瘤作用。ADC的主要问题是出现干扰疗效的事件和脱靶细胞毒性。双特异性抗体构建体是即用型疗法,其特点是可能很快就能获得。双特异性抗体构建体最关键的局限性是它们的半衰期短,需要长时间静脉输注。CAR-T细胞在经过大量预处理的复发/难治性MM(RRMM)中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、血细胞减少和低丙种球蛋白血症。需要进一步研究以确定哪些合格患者能从一种治疗中比另一种治疗中获益更多。

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