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非霍奇金淋巴瘤 CAR-T 细胞治疗应答的炎症生物标志物特征

英文原题:An inflammatory biomarker signature of response to CAR-T cell therapy in non-Hodgkin lymphoma.

查看英文原题

An inflammatory biomarker signature of response to CAR-T cell therapy in non-Hodgkin lymphoma.

PubMed 2025/04/01(内容时间) Nat Med Q1 · IF 52.5(JCR 2025)

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中文摘要

非霍奇金淋巴瘤(NHL)患者接受CAR-T(CAR-T)细胞治疗时,疾病进展仍是重大挑战。本文提出 InflaMix(炎症混合模型),这是一种无监督定量模型,整合输注 CAR-T 前测得的 14 项实验室及细胞因子指标,以反映炎症和终末器官功能。研究使用 149 例 NHL 患者队列开发模型;InflaMix 揭示了一种与 CAR-T 治疗失败高风险相关的炎症特征,包括死亡或复发风险升高(风险比 2.98,95% 置信区间 1.60–4.91,P < 0.001)。来自不同治疗中心、共 688 例 NHL 患者的 3 个独立队列用于验证该方法。InflaMix 持续且可重复地识别出更可能疾病复发和死亡的患者,并在已确立预后标志物(包括肿瘤负荷)之外提供额外预测价值。该模型在数据缺失病例中也表现稳健;仅考虑 6 项易于获取的实验室指标时,仍能维持准确性。研究结果表明,InflaMix 是 NHL 患者接受 CAR-T 治疗时可用于床旁临床决策的有价值工具。

展开英文摘要原文

Disease progression is a substantial challenge in patients with non-Hodgkin lymphoma (NHL) undergoing chimeric antigen receptor T cell (CAR-T) therapy.

Here we present InflaMix (INFLAmmation MIXture Model), an unsupervised quantitative model integrating 14 pre-CAR-T infusion laboratory and cytokine measures capturing inflammation and end-organ function. Developed using a cohort of 149 patients with NHL, InflaMix revealed an inflammatory signature associated with a high risk of CAR-T treatment failure, including increased hazard of death or relapse (hazard ratio, 2.

98; 95% confidence interval, 1. 60-4. 91; P < 0. 001). Three independent cohorts comprising 688 patients with NHL from diverse treatment centers were used to validate our approach. InflaMix consistently and reproducibly identified patients with a higher likelihood of disease relapse and mortality, and it provided supplementary predictive value beyond established prognostic markers, including tumor burden.

Moreover, InflaMix exhibited robust performance in cases with missing data, maintaining accuracy when considering only six readily available laboratory measures.

These findings show that InflaMix is a valuable tool for point-of-care clinical decision-making in patients with NHL undergoing CAR-T therapy.

论文信息

作者
Raj SS、Fei T、Fried S、Ip A、Fein JA、Leslie LA、Alarcon Tomas A、Leithner D
第一作者单位
Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.United States
通讯作者单位
Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. shouvalr@mskcc.org.United States
期刊
Nature medicine2025 Apr
原文标识
PubMed 40169864 · DOI 10.1038/s41591-025-03532-x