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重新思考 BCMA 靶向治疗的神经毒性机制

英文原题:Rethinking mechanisms of neurotoxicity with BCMA directed therapy.

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Rethinking mechanisms of neurotoxicity with BCMA directed therapy.

PubMed 2021/08/27(内容时间) Crit Rev Oncol Hematol Q1 · IF 6.2(JCR 2025)

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中文摘要

B细胞成熟抗原(BCMA)已成为多发性骨髓瘤中抗体药物偶联物、双特异性抗体、CAR-T 细胞疗法及其他免疫治疗的关键靶点。其中一些药物,如belantamab mafodotin和idecabtagene vicleucel,已在美国获得监管批准。尽管BCMA通常被认为几乎仅表达于浆细胞,且靶向脱肿瘤毒性的可能性较低,但在BCMA免疫治疗的谱系中已观察到一系列不寻常的神经毒性。在某些病例中,这些不寻常的神经毒性表现已导致患者死亡或药物退出进一步开发。本综述总结了该领域的文献,并强调了由于BCMA在神经组织中的表达而可能出现的靶向毒性。我们提请注意有必要对这些毒性进行进一步研究。随着BCMA靶向治疗被推进至更早期的治疗线,这一风险变得日益重要。

展开英文摘要原文

B-cell maturation antigen (BCMA) has become a key target for antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor T-cell therapies, and other immunotherapies in multiple myeloma. Some of these agents such as belantamab mafodotin and idecabtagene vicleucel have already received regulatory approval in the United States.

Although BCMA has generally been considered to be expressed almost exclusively in plasma cells with a low likelihood of on-target off-tumor toxicity, there has been a range of unusual neurotoxicity observed across the spectrum of BCMA immunotherapies. In certain cases, these unusual neurotoxicity presentations have led to patient death or withdrawal of agents from further development.

Our review summarizes the literature in this field and highlights the possibility of on-target toxicities due to neural expression of BCMA.

We draw attention to the need for further investigation of these toxicities. This risk becomes increasingly important as BCMA targeted therapies are brought to earlier lines of treatment.

论文信息

作者
Mohyuddin GR、Banerjee R、Alam Z、Berger KE、Chakraborty R
单位
Department of Hematology and Hematological Malignancies, Huntsman Cancer Center, University of Utah, United States. Electronic address: g.mohyuddin@hci.utah.edu.United States
文献类型
综述
期刊
Critical reviews in oncology/hematology2021 Oct
原文标识
PubMed 34461271 · DOI 10.1016/j.critrevonc.2021.103453

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