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BCMA 靶向治疗、骨髓瘤治疗工具箱中的新疗法及其使用方式

英文原题:BCMA-directed therapy, new treatments in the myeloma toolbox, and how to use them.

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BCMA-directed therapy, new treatments in the myeloma toolbox, and how to use them.

PubMed 2023/11/21(内容时间) Leuk Lymphoma Q3 · IF 2.1(JCR 2025)

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中文摘要

为解决复发难治性多发性骨髓瘤(RRMM)治疗选择匮乏的问题,研究焦点已转向免疫治疗策略,其中大多数在研产品靶向B细胞成熟抗原(BCMA)。BCMA是肿瘤坏死因子受体超家族的跨膜受体,对浆细胞存活至关重要,在非造血组织中表达极低;它是一个理想的治疗靶点。靶向BCMA的治疗分为三类,各有优劣。抗体药物偶联物(ADC)可即时获得,在RRMM中单药疗效中等,但角膜毒性限制了其可递送性。CAR-T 细胞是最有效的一类,但面临显著的物流和经济障碍。双特异性抗体相比ADC具有更优的疗效和耐受性,但 prolonged exposure 会导致显著的累积感染风险。在本综述中,我们将探讨BCMA在MM生物学中的作用、已获批和新兴的靶向该抗原的治疗,以及如何优化这些药物的序贯使用。

展开英文摘要原文

To address the dearth of therapeutic options available for relapsed-refractory multiple myeloma (RRMM), attention has shifted to immunotherapeutic strategies, with most products in development targeting the B-cell maturation antigen (BCMA). BCMA is a transmembrane receptor of the tumor necrosis factor receptor superfamily, essential for plasma cell survival and minimally expressed on non-hematopoietic tissues; it represents an ideal therapeutic target. Three categories of BCMA-directed therapies exist, with distinct strengths and weaknesses.

Antibody-drug conjugates (ADCs) are immediately available with modest single-agent efficacy in RRMM, but deliverability is hampered by corneal toxicity. CAR T-cells are the most effective class but face significant logistical and financial barriers.

Bispecific antibodies offer superior efficacy and tolerability compared to ADCs, but prolonged exposure causes significant cumulative infectious risk. In this review, we will examine the role of BCMA in MM biology, the approved and emerging therapies targeting this antigen, and how these agents can be optimally sequenced.

论文信息

作者
Rees MJ、Kumar S
单位
Division of Hematology, Mayo Clinic, Rochester, MN, USA.United States
文献类型
综述 · 非美国政府资助研究
期刊
Leukemia & lymphoma2024 Mar
原文标识
PubMed 38354090 · DOI 10.1080/10428194.2023.2284088