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.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
Δ-β2M 作为预测 CAR-T 细胞治疗后 ICU 入住的动态生物标志物
英文原题：Δ-β2M as a dynamic biomarker for predicting ICU admission after CAR T-cell therapy.
查看英文原题
Δ-β2M as a dynamic biomarker for predicting ICU admission after CAR T-cell therapy.
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中文摘要
CAR-T 细胞疗法可能引起危及生命的毒性，需入住重症监护病房（ICU）。目前缺乏可用于早期风险分层的可靠生物标志物。本研究评估β2-微球蛋白（β2M）能否作为动态生物标志物预测CAR-T 细胞治疗后的ICU入住。研究为单中心回顾性研究，包括建模队列（2020–2023年，n=97）及两个时间上独立的验证队列（2024年，n=38；2025年，n=23）。β2M变化量（原文符号显示缺失）按输注时（T2）至第+3天（T3）的变化计算。主要终点为ICU入住。采用受试者工作特征（ROC）分析、校准评估（Hosmer-Lemeshow检验、Brier评分）和决策曲线分析评估预测性能。建模队列、2024年队列和2025年队列分别有54、17和17例患者具备完整β2M数据。
β2M变化量在所有队列中均能稳定区分是否入住ICU（建模队列AUC=0.67；2024年AUC=0.70；2025年AUC=0.82），但不能预测免疫效应细胞相关神经毒性综合征（ICANS）（AUC=0.53）。模型校准良好（Hosmer-Lemeshow检验P=0.073；Brier评分0.232），并经交叉验证确认（Brier评分0.236）。决策曲线分析显示，在临床相关阈值（0.20–0.70）范围内具有正向净获益。基线参数（白蛋白、CRP、NT-proBNP）未能在验证队列中表现出一致性。β2M是易于测量的动态生物标志物，与CAR-T 细胞治疗后ICU入住相关，且具有良好校准度和临床效用。这些结果支持进一步评估早期生物标志物动力学在毒性风险预测模型中的作用。
展开英文摘要原文
CAR T-cell therapy is associated with life-threatening toxicities requiring intensive care unit (ICU) admission. Reliable biomarkers for early risk stratification are lacking.
We evaluated - 2-microglobulin ( - 2M) as a dynamic biomarker for predicting ICU admission after CAR T-cell therapy. Single-center retrospective study with a derivation cohort (2020-2023, n = 97) and two temporally independent validation cohorts (2024, n = 38; 2025, n = 23). - 2M was calculated as the change between infusion (T2) and day +3 (T3). Primary endpoint was ICU admission. Predictive performance was assessed using receiver operating characteristic (ROC) analysis, calibration (Hosmer-Lemeshow test, Brier score), and decision curve analysis. Complete - 2M data were available in 54 (derivation), 17 (2024), and 17 (2025) patients.
- 2M demonstrated consistent discrimination for ICU admission across all cohorts (derivation AUC 0. 67; 2024 AUC 0. 70; 2025 AUC 0. 82), but not for immune effector cell associated neurotoxicity syndrome (ICANS) (AUC 0. 53). The model showed good calibration (Hosmer-Lemeshow p = 0. 073; Brier score 0. 232), confirmed by cross-validation (Brier score 0.
236). Decision curve analysis revealed positive net benefit across clinically relevant thresholds (0. 20-0. 70). Baseline parameters (albumin, CRP, NT-proBNP) lacked consistent validation. - 2M is an easily measurable dynamic biomarker associated with ICU admission after CAR T-cell therapy, with good calibration and clinical utility.
These findings support further evaluation of early biomarker kinetics in toxicity risk prediction models.
论文信息
- 作者
- Angleitner AC、Maulhardt M、Thomson K、Büntzel J、Wulf G
- 单位
- Department of Hematology and Medical Oncology, University Medical Center Göttingen, Robert-Koch-Strasse 40, Göttingen, Lower Saxony, 37075, Germany. alexander.angleitner@med.uni-goettingen.de.Germany
- 期刊
- Annals of hematology2026 May 26
- 原文标识
- PubMed 42192014 · DOI 10.1007/s00277-026-07075-0
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