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确定CAR T细胞治疗效率和安全性的修饰剂:系统性审查和个人患者数据元分析

Manoj M Lalu¹, Samuel Igweokpala², Natasha Kekre³

¹Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada.

Transfusion medicine reviews

|April 25, 2025

概括

患者因素显著影响血液癌症中CAR T细胞治疗结果. 结合目标和使用全源细胞可以改善完整的反应并减少神经毒性,优化CAR T细胞的疗效和安全.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
血液学恶性瘤是什么

背景情况:

化学抗原受体 (CAR) T细胞疗法在复发性/耐药性血液性恶性瘤中显示出有效性.
由于患者和与治疗有关的因素,治疗结果具有很大的变化.
了解这些因素对于优化CAR T细胞治疗至关重要.

研究的目的:

在血液恶性瘤中进行CAR T细胞治疗的个体患者数据元分析 (IPDMA).
确定改变治疗疗效和安全结果的患者层面因素.
探索特定修饰剂与完整反应,细胞因子释放综合征 (CRS) 和免疫效应细胞相关的神经毒性综合征 (ICANS) 之间的关联.

主要方法:

在MEDLINE,Embase和Cochrane CENTRAL系统搜索相关的CAR T细胞治疗试验.
从89个已识别的试验中收集和汇集个人患者数据 (IPD),包括2,331名患者.
分析潜在的修饰因素的层面的完整反应率,CRS和ICANS流行率.

主要成果:

根据癌症类型,完全响应率从25%到75%不等.
桥梁治疗和自身细胞来源与没有桥梁治疗和异构源相比,完全反应的减少有关.
多位CAR-T细胞疗法 (例如CD19加其他) 显示出比单独CD19疗法更高的响应率.
自主细胞来源增加了ICANS的风险,而非异性源.
桥接疗法,CAR T细胞源/点,性别,年龄,细胞输液数,共刺激域和剂量影响了安全性和疗效.

结论:

患者和治疗特异性因素显著改变了血液恶性瘤中CAR T细胞治疗的疗效和安全性.
异构细胞源和多目标CAR T细胞结构可能提供更好的反应和安全概况.
对优化这些修饰物的进一步研究是有必要的,以提高患者的治疗结果.

关键词:

用CAR T细胞疗法进行治疗.完成一个完整的响应.细胞因子释放综合征细胞因子释放综合征有效性有效性.血液学血液学在ICANS中,我们可以看到ICANS.个体患者数据的元分析.在瘤学瘤学.安全的安全的安全的安全的安全.系统性审查系统性审查

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