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cilta-cel 治疗后的慢性炎性脱髓鞘性多神经病(CIDP)

英文原题:Chronic inflammatory demyelinating polyneuropathy (CIDP) after cilta-cel therapy.

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Chronic inflammatory demyelinating polyneuropathy (CIDP) after cilta-cel therapy.

PubMed 2025/10/20(内容时间) Blood Cancer J Q1 · IF 13.8(JCR 2025)

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中文摘要

Ciltacabtagene autoleucel(cilta-cel)是一种对复发/难治性多发性骨髓瘤具有高度活性的CAR-T 细胞疗法,但可能诱发严重的免疫介导毒性。本文介绍2例接受cilta-cel后发生慢性炎性脱髓鞘性多发性神经病(CIDP)的患者。患者1在输注后112天出现步态共济失调迅速进展、弛缓性轻瘫和动眼神经麻痹;患者2于第19天出现类似综合征。两例患者的肌电图和神经传导检查均证实感觉运动性轴索-脱髓鞘性神经病;脑MRI和脑脊液感染检测均无异常。血液和脑脊液中均可检测到CAR-T 细胞,但以CD8非CAR-T 细胞为主。TCR测序显示,患者1存在高度扩增的克隆(约占全部测序读段的30%),患者2则为多克隆受体库。大剂量地塞米松联合静脉注射免疫球蛋白未能改善神经症状,因此给予可清除T细胞的环磷酰胺治疗,CAR及非CAR-T 细胞数量均随之下降。患者1因呼吸衰竭死亡,患者2病情改善并出院。这些观察表明,CIDP是cilta-cel治疗的一种严重并发症,可能由自身反应性CD8 T细胞旁观者扩增所致,而非CAR-T 细胞的直接作用。及时升级至清除T细胞的治疗可能改善结局。

展开英文摘要原文

Ciltacabtagene-autoleucel (cilta-cel) is a CAR-T cell therapy highly active in relapsed/refractory multiple myeloma but can induce severe immune-mediated toxicities.

We describe two patients who developed chronic inflammatory demyelinating polyneuropathy (CIDP) after cilta-cel. Patient 1 presented with rapidly progressive gait ataxia, flaccid paraparesis, and oculomotor palsy 112 days post infusion; Patient 2 developed an analogous syndrome on day 19. In both patients, electromyography and nerve-conduction studies confirmed sensorimotor axonal-demyelinating neuropathy; brain MRI and CSF infection panels were unremarkable. CAR-T cells were detectable in blood and CSF, yet a predominance of CD8 non-CAR-Tcells was observed.

TCR- sequencing revealed a hyper-expanded clone (~30% of all reads) in patient 1 versus a polyclonal repertoire in patient 2. High-dose dexamethasone plus intravenous immunoglobulin failed to improve neurologic symptoms and prompted T-cell-depleting cyclophosphamide, which lowered CAR- and non-CAR-T cells.

Patient 1 died from respiratory failure, whereas patient 2 improved and could be discharged. These observations indicate that CIDP is a severe complication of cilta-cel therapy and may arise from bystander expansion of autoreactive CD8 T-cells rather than direct CAR-T cell activity. Timely escalation to T-cell-depleting therapy may improve outcomes.

论文信息

作者
Korenkov M、Liebaert J、Yousefian S、Schwartz S、Demel UM、Braune J、Odabasi MC、Herzberg L
第一作者单位
Department of Hematology, Oncology and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität and Humboldt-Universität zu Berlin, Berlin, Germany.Germany
通讯作者单位
Department of Hematology, Oncology and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität and Humboldt-Universität zu Berlin, Berlin, Germany. antonia.busse@charite.de.Germany
文献类型
病例报告 · 读者来信
期刊
Blood cancer journal2025 Oct 20
原文标识
PubMed 41115887 · DOI 10.1038/s41408-025-01384-9