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早期评估严重免疫检查点抑制剂相关心肌炎:真实世界的临床实践。

Early evaluation of severe immune checkpoint inhibitor-associated myocarditis: a real-world clinical practice.

机构信息

Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

J Cancer Res Clin Oncol. 2023 Sep;149(11):8345-8357. doi: 10.1007/s00432-023-04782-3. Epub 2023 Apr 19.

Abstract

PURPOSE

Immune checkpoint inhibitor (ICI)-associated myocarditis is a rare but severe complication for patients treated with immunotherapy. This study aims to explore the predictive significance of patients' clinical features and examination results for the severity of ICI-associated myocarditis.

METHODS

Data from a real-world cohort of 81 cancer patients who developed ICI-associated myocarditis after immunotherapy were retrospectively analyzed. The development of myocarditis of Common Terminology Criteria for Adverse Events (CTCAE) grades 3-5 and/or the major adverse cardiovascular event (MACE) was set as endpoints. Logistic regression was used to evaluate the predictive value of each factor.

RESULTS

CTCAE grades 3-5 and MACE developed in 43/81 (53.1%) and 28/81 (34.6%) cases, respectively. The likelihood of CTCAE grades 3-5 and MACE increased with the accumulation of organs affected by the ICI-associated adverse events and initial clinical symptoms. Concurrent systematic therapies during ICI treatment did not raise the risk of myocarditis severity, while prior chemotherapy did. Besides classical serum cardiac markers, a higher neutrophil ratio was also related to poorer cardiac outcomes, whereas higher lymphocyte and monocyte ratios were predictors of favorable cardiac outcomes. The CD4+ T cell ratio and CD4/CD8 ratio were negatively related to CTCAE grades 3-5. Several cardiovascular magnetic resonance parameters were associated with myocarditis severity, whereas the predictive value of echocardiography and electrocardiogram was weak.

CONCLUSION

This study comprehensively evaluated the prognostic value of patients' clinical characteristics and examination results and identified several predictors of severe ICI-associated myocarditis, which will facilitate early detection of severe ICI-associated myocarditis in patients receiving immunotherapy.

摘要

目的

免疫检查点抑制剂(ICI)相关性心肌炎是接受免疫治疗的患者的一种罕见但严重的并发症。本研究旨在探讨患者的临床特征和检查结果对 ICI 相关性心肌炎严重程度的预测意义。

方法

回顾性分析了 81 例接受免疫治疗后发生 ICI 相关性心肌炎的癌症患者的真实世界队列数据。以 Common Terminology Criteria for Adverse Events(CTCAE)分级 3-5 和/或主要不良心血管事件(MACE)的发生为终点。采用逻辑回归评估各因素的预测价值。

结果

81 例患者中,分别有 43 例(53.1%)和 28 例(34.6%)发生 CTCAE 分级 3-5 和 MACE。ICI 相关不良事件累及器官的数量和初始临床症状的积累使发生 CTCAE 分级 3-5 和 MACE 的可能性增加。ICI 治疗期间同时进行系统治疗并不会增加心肌炎严重程度的风险,而先前的化疗则会增加这种风险。除了经典的血清心脏标志物外,较高的中性粒细胞比例也与较差的心脏结局相关,而较高的淋巴细胞和单核细胞比例是心脏结局良好的预测因子。CD4+T 细胞比例和 CD4/CD8 比值与 CTCAE 分级 3-5 呈负相关。一些心血管磁共振参数与心肌炎严重程度相关,而心电图和超声心动图的预测价值较弱。

结论

本研究全面评估了患者临床特征和检查结果的预后价值,确定了一些预测严重 ICI 相关性心肌炎的指标,这将有助于在接受免疫治疗的患者中早期发现严重的 ICI 相关性心肌炎。

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