CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Simple and early prediction of severe CAR-T-related adverse events after Axi-cel infusion by initial high fever.
Simple and early prediction of severe CAR-T-related adverse events after Axi-cel infusion by initial high fever.
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CAR-T 细胞相关不良事件(CAR-AEs),如免疫效应细胞相关神经毒性综合征(ICANS)和细胞因子释放综合征(CRS),可能危及生命,并可能需要大剂量类固醇治疗。以简化的方式识别严重CAR-AEs高风险患者对于早期治疗干预至关重要。这项回顾性研究分析了44例接受axicabtagene ciloleucel(Axi-cel)治疗的患者,以确定严重CAR-AEs的预测因素。
我们发现,3级ICANS、噬血细胞综合征和ICU入住与更需要大剂量类固醇相关,我们将其定义为与大剂量类固醇相关的事件(EHS)。在CAR-T 输注后24 h内出现初始发热(38.6 C)的患者中,EHS的发生率显著更高(p < 0.001)。与无EHS的患者相比,有EHS的患者的无进展生存期(PFS)显著更短(p < 0.001)。
此外,在24 h内出现发热的患者以及峰值发热为38.6 C的患者,其峰值CAR-T 计数均往往高于其他患者。我们的研究结果表明,Axi-cel输注后24 h内的初始发热(38.6 C)可能预测需要大剂量类固醇治疗的严重CAR-AEs,并且EHS与更差的PFS相关。
Chimeric antigen receptor T-cell (CAR-T)-related adverse events (CAR-AEs), such as immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS), can be life-threatening and may require high-dose steroids. Identifying patients at high risk for severe CAR-AEs in a simplified way is crucial for early therapeutic intervention. This retrospective study analyzed 44 patients treated with axicabtagene ciloleucel (Axi-cel) to identify predictive factors for severe CAR-AEs.
We found that grade 3 ICANS, hemophagocytic syndrome, and ICU admission were associated with a greater need for high-dose steroids, which we defined as events associated with high-dose steroids (EHS). The incidence of EHS was significantly higher in patients who developed an initial fever ( 38. 6 C) within 24 h of CAR-T infusion (p < 0. 001). Progression-free survival (PFS) was significantly shorter in patients with EHS compared to those without EHS (p < 0. 001).
Additionally, patients who developed a fever within 24 h and those with a peak fever of 38. 6 C both tended to have higher peak CAR-T counts compared to other patients.
Our findings suggest that an initial fever ( 38. 6 C) within 24 h of Axi-cel infusion may predict severe CAR-AEs requiring high-dose steroids, and that EHS is associated with worse PFS.
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