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BCMA 靶向 CAR-T 细胞治疗后出现伴帕金森综合征特征的神经认知与运动减少性运动障碍

英文原题:Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy.

查看英文原题

Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy.

PubMed 2021/12/10(内容时间) Nat Med Q1 · IF 52.5(JCR 2025)

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中文摘要

B细胞成熟抗原(BCMA)是多发性骨髓瘤(MM)嵌合抗原受体(CAR)T细胞治疗的重要肿瘤相关靶点。本文描述一例MM患者,该患者参加CARTITUDE-1试验(NCT03548207),在输注靶向BCMA的ciltacabtagene autoleucel CAR-T 细胞后约3个月出现进行性运动障碍并呈帕金森综合征特征;同时,血液和脑脊液中可见CAR-T 细胞持续存在,基底节有淋巴细胞浸润。

我们在患者基底节神经元和星形胶质细胞上发现BCMA表达。公开转录组数据集进一步证实正常人脑尾状核中存在BCMA RNA表达,提示这可能是抗BCMA治疗的靶向相关效应。考虑到II期ciltacabtagene autoleucel试验中有3例患者报告3级及以上帕金森综合征,且idecabtagene vicleucel说明书中也报告了3级帕金森综合征,我们的发现支持对接受BCMA靶向T细胞治疗的患者进行密切神经系统监测。

展开英文摘要原文

B-cell maturation antigen (BCMA) is a prominent tumor-associated target for chimeric antigen receptor (CAR)-T cell therapy in multiple myeloma (MM).

Here, we describe the case of a patient with MM who was enrolled in the CARTITUDE-1 trial ( NCT03548207 ) and who developed a progressive movement disorder with features of parkinsonism approximately 3 months after ciltacabtagene autoleucel BCMA-targeted CAR-T cell infusion, associated with CAR-T cell persistence in the blood and cerebrospinal fluid, and basal ganglia lymphocytic infiltration.

We show BCMA expression on neurons and astrocytes in the patient's basal ganglia. Public transcriptomic datasets further confirm BCMA RNA expression in the caudate of normal human brains, suggesting that this might be an on-target effect of anti-BCMA therapy. Given reports of three patients with grade 3 or higher parkinsonism on the phase 2 ciltacabtagene autoleucel trial and of grade 3 parkinsonism in the idecabtagene vicleucel package insert, our findings support close neurological monitoring of patients on BCMA-targeted T cell therapies.

论文信息

作者
Van Oekelen O、Aleman A、Upadhyaya B、Schnakenberg S、Madduri D、Gavane S、Teruya-Feldstein J、Crary JF
第一作者单位
Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.United States
通讯作者单位
Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. samir.parekh@mssm.edu.United States
文献类型
美国 NIH 资助研究 · 非美国政府资助研究
期刊
Nature medicine2021 Dec
原文标识
PubMed 34893771 · DOI 10.1038/s41591-021-01564-7