一个阶段1/2研究的捐赠者衍生的抗CD33CART细胞疗法 (VCAR33) 复发/耐药AML后异构HCT后
Muhammad Umair Mushtaq1, John F DiPersio2, Jacques Azzi3
1University of Kansas Medical Center, Westwood, Kansas, United States.
Blood
|February 4, 2026
概括
VCAR33是一种CD33导向的CAR T细胞疗法,在移植后治疗复发性急性髓性白血病 (AML) 和骨髓质综合征 (MDS) 方面表现有前途. 该疗法在1/2期临床研究中显示出可接受的安全性和初步的抗白血病活性.
科学领域:
- 免疫治疗是一种免疫疗法.
- 血液瘤学 血液瘤学
- 细胞疗法细胞疗法
背景情况:
- 在异性造血细胞移植 (alloHCT) 后复发或不耐药的急性髓性白血病 (AML) 和骨髓失质综合征 (MDS) 的预后不好.
- CD33是一种在AML和MDS细胞表达的抗原.
- 化学抗原受体 (CAR) T细胞疗法提供了一种潜在的策略来克服治疗耐药性.
研究的目的:
- 评估VCAR33的安全性和有效性,一种来自供体的CD33定向的CAR T细胞产品,在患有复发或可测量的残留疾病 (MRD) CD33+ AML/MDS阳性的成年人中.
- 评估用于抗瘤监测的VCAR33构造的临床前特征.
主要方法:
- 进行了一项1/2期临床研究,涉及15名患有复发或MRD阳性CD33+AML/MDS的成年患者.
- 患者接受了VCAR33的两种剂量水平 (DL1和DL2),按疾病负担分层.
- 通过监测与治疗相关的不良事件,包括细胞因子释放综合征和神经毒性来评估安全性. 通过总体响应率和MRD清除值来评估有效性. 还监控了VCAR33的扩张.
主要成果:
- 最常见的与治疗相关的不良事件是细胞因子释放综合征 (93.3%),所有事件都低于3级.
- 免疫细胞相关的神经毒性综合征发生在26.7%的患者 (1事件≥3级).
- 观察到20%的整体应答率,在3名患者中实现了完全缓解或MRD清除. 在93.3%的患者中发现过渡性VCAR33扩张.
结论:
- 全基性CAR T产品VCAR33在alloHCT后在复发或MRD阳性AML/MDS患者中显示出可接受的安全性和初步的抗白血病活性.
- VCAR33值得进一步研究作为维持疗法,以降低高风险AML/MDS患者移植后复发风险.
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