在高风险的老年患者中ICANS缓解治疗CD28共刺激抗CD19CAR-T细胞使用标准化协议:试点研究
Gil Fridberg1, Odelia Amit2, Yehonathan Sherf3
1BMT and Cellular Therapy Unit, Hematology Division, Aviv Sourasky Medical Center; Gray Faculty of Medical and Health Sciences, Aviv University, Aviv. gilfr@tlvmc.gov.il.
Haematologica
|February 12, 2026
概括
使用 levetiracetam,thiamine和早期类固醇/anakinra的新协议减少了老年人接受基于CD28的CAR-T治疗LBCL的神经毒性 (ICANS) 持续时间.
科学领域:
- 在瘤学瘤学.
- 神经学 神经学
- 免疫治疗是一种免疫疗法.
背景情况:
- 化学抗原受体T细胞 (CAR-T) 疗法,特别是基于CD28的产品,已经彻底改变了复发性/耐药性大B细胞淋巴瘤 (LBCL) 治疗.
- 然而,这些疗法与免疫效应细胞相关的神经毒性综合征 (ICANS) 的高发病率有关,特别是在缺乏特定缓解策略的老年人中.
- 现有的数据显示,经批准的基于CD28的CAR-T剂的整体和严重ICANS率分别为78%和35%.
研究的目的:
- 开发和实施一个标准化的ICANS缓解协议,适用于接受基于CD28的抗CD19CAR-T治疗的老年人.
- 为解决这一脆弱患者群体中管理神经毒性的关键未满足需求.
主要方法:
- 一个单臂前性试点研究对75岁或以上的患者进行,或65岁或以上的患者有额外的危险因素,接受基于CD28的CAR-T.
- 该协议包括了 levetiracetam 和胺预防.
- 早期,基于等级的皮质类固醇和anakinra的使用用于3级或更高的耐火性ICANS (定义为24小时内没有改善).
主要成果:
- 纳入了45名患者,平均年龄为75岁;78%的ECOG表现状态为2或更高,42%的患者有先前存在的神经相关疾病.
- 该协议导致整体,等级3或更高,耐火ICANS率分别为67%,31%和20%.
- ICANS的平均持续时间为4天,与历史队伍相比,时间更短. 疾病特征没有预测ICANS指标,尽管LDH显示出严重ICANS的趋势.
结论:
- 实施的标准化协议有效地减少了接受基于CD28的CAR-T治疗的老年人ICANS的持续时间.
- 这些发现表明,主动的神经保护策略可以减轻易受伤害的老年人群中与CAR-T相关的神经毒性.
- 需要进一步的研究来证实这些发现并优化管理策略,考虑到累积类固醇与感染增加和非复发死亡率的关联.
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