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抗体药物偶联物贝兰他单抗莫福汀治疗多发性骨髓瘤的综合综述

The Antibody Drug Conjugate, Belantamab-Mafodotin, in the Treatment of Multiple Myeloma: A Comprehensive Review.

作者信息

Almodovar Diaz Adrian Alfonso, Alouch Samhar Samer, Chawla Yogesh, Gonsalves Wilson I

机构信息

Division of Hematology, Mayo Clinic, Rochester, MN, USA.

出版信息

Blood Lymphat Cancer. 2024 Dec 6;14:71-87. doi: 10.2147/BLCTT.S490021. eCollection 2024.

Abstract

Despite recent advancements in treatments, including proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains mostly incurable with patients frequently experiencing disease relapses due to therapy resistance. Hence there is an urgent need for innovative treatments for patients with relapsed and/or refractory MM (RRMM). This review examines Belantamab mafodotin, the first antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA), which has shown efficacy in pre-clinical and clinical settings for RRMM. BCMA, a type III transmembrane glycoprotein critical for B cell functions, is predominantly expressed in malignant plasma cells making it a promising therapeutic target. ADCs, comprising a monoclonal antibody, a cytotoxic payload, and a linker, offer a targeted and potent therapeutic approach to cancer treatment. Belantamab mafodotin integrates an afucosylated monoclonal antibody and monomethyl auristatin F (MMAF) as its cytotoxic agent. It induces apoptosis in MM cells by disrupting microtubule formation and interfering with important signaling pathways. The series of DREAMM (Driving Excellence in Approaches to MM) studies have extensively evaluated Belantamab mafodotin in various clinical settings. This review provides a comprehensive overview of pre-clinical and clinical data supporting Belantamab mafodotin as a future therapeutic option for RRMM.

摘要

尽管近期在治疗方面取得了进展,包括蛋白酶体抑制剂、免疫调节剂和抗CD38单克隆抗体,但多发性骨髓瘤(MM)大多仍无法治愈,患者常因治疗耐药而出现疾病复发。因此,迫切需要为复发和/或难治性MM(RRMM)患者提供创新治疗方法。本综述考察了贝利司他单抗(Belantamab mafodotin),这是首个靶向B细胞成熟抗原(BCMA)的抗体药物偶联物(ADC),已在RRMM的临床前和临床环境中显示出疗效。BCMA是一种对B细胞功能至关重要的III型跨膜糖蛋白,主要在恶性浆细胞中表达,使其成为一个有前景的治疗靶点。ADC由单克隆抗体、细胞毒性载荷和连接子组成,为癌症治疗提供了一种靶向且有效的治疗方法。贝利司他单抗整合了一种去岩藻糖基化单克隆抗体和单甲基奥瑞他汀F(MMAF)作为其细胞毒性药物。它通过破坏微管形成和干扰重要信号通路诱导MM细胞凋亡。一系列DREAMM(推动MM治疗卓越进展)研究已在各种临床环境中广泛评估了贝利司他单抗。本综述全面概述了支持贝利司他单抗作为RRMM未来治疗选择的临床前和临床数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a37b/11631777/85144c98189b/BLCTT-14-71-g0001.jpg

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