免疫相关不良事件中糖皮质激素及免疫抑制剂管理策略对患者生存结局的影响：系统评价与Meta分析

兰欣悦; 周奕成; 陈东芹

doi:10.19401/j.cnki.1007-3639.2025.10.002

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免疫相关不良事件中糖皮质激素及免疫抑制剂管理策略对患者生存结局的影响：系统评价与Meta分析

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- 免疫相关不良事件中糖皮质激素及免疫抑制剂管理策略对患者生存结局的影响：系统评价与Meta分析
- Survival impact of corticosteroid and immunosuppressant management strategies for immune-related adverse events in immune checkpoint inhibitor-treated patients: a systematic review and meta-analysis
- 中国癌症杂志 2025年35卷第10期页码：906-919
- 作者机构：
  
  上海交通大学医学院附属仁济医院肿瘤科，上海 200032
- 作者简介：
  
  [ "兰欣悦（ORCID: 0009-0009-3247-9769），上海交通大学医学院附属仁济医院在读硕士研究生。" ]
  [ "陈东芹，博士、博士后、主任医师、上海交通大学医学院博士研究生导师，现任上海交通大学医学院附属仁济医院肿瘤科行政副主任。担任教育部学位中心学位论文评审专家，国家自然科学基金、中国博士后科学基金评审专家；此外，还担任国家药品独立数据监查委员会（IDMC）委员，中国医师协会肿瘤医师分会肺癌学组、多原发/不明原发灶肿瘤学组委员，中国临床肿瘤学会非小细胞肺癌、小细胞肺癌、血管靶向治疗专家委员会委员，中国抗癌协会整合肿瘤肾脏病专业委员会委员，上海市医学会肿瘤专委会青年委员会副主任委员，长三角肿瘤专科联盟专家委员会常务副秘书长及理事，上海市抗癌协会疑难肿瘤、抗肿瘤药物安全管理专业委员会委员。承担国家自然科学基金项目3项、省部级课题3项。以第一作者/通信作者在Drug Resistance Updates、Molecular Cancer等期刊发表论文10余篇。" ]
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2025.10.002
  中图分类号： R730.51
- 收稿：2025-06-24，
  
  修回：2025-09-16，
  
  纸质出版：2025-10-30
- 稿件说明：
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兰欣悦, 周奕成, 陈东芹. 免疫相关不良事件中糖皮质激素及免疫抑制剂管理策略对患者生存结局的影响：系统评价与Meta分析[J]. 中国癌症杂志, 2025,35(10):906-919.

Xinyue LAN, Yicheng ZHOU, Dongqin CHEN. Survival impact of corticosteroid and immunosuppressant management strategies for immune-related adverse events in immune checkpoint inhibitor-treated patients: a systematic review and meta-analysis[J]. China Oncology, 2025, 35(10): 906-919.
兰欣悦, 周奕成, 陈东芹. 免疫相关不良事件中糖皮质激素及免疫抑制剂管理策略对患者生存结局的影响：系统评价与Meta分析[J]. 中国癌症杂志, 2025,35(10):906-919. DOI： 10.19401/j.cnki.1007-3639.2025.10.002.

Xinyue LAN, Yicheng ZHOU, Dongqin CHEN. Survival impact of corticosteroid and immunosuppressant management strategies for immune-related adverse events in immune checkpoint inhibitor-treated patients: a systematic review and meta-analysis[J]. China Oncology, 2025, 35(10): 906-919. DOI： 10.19401/j.cnki.1007-3639.2025.10.002.

摘要

免疫检查点抑制剂（immune checkpoint inhibitor，ICI）已经彻底革新了肿瘤治疗，但其应用常伴随免疫相关不良事件（immune-related adverse event，irAE），需要使用糖皮质激素或二线免疫抑制剂予以处理。然而，这些治疗策略对irAE患者预后的影响及其机制尚不清楚。本系统评价与Meta分析旨在评估irAE患者中糖皮质激素及二线免疫抑制剂的使用对生存结局的影响。检索PubMed、Embase、Web of Science、Cochrane Library、SinoMed、CNKI、万方数据库，纳入近10年（至2025年5月）发表的关于ICI相关irAE患者中激素及免疫抑制剂使用对生存结局影响的观察性研究（回顾性/前瞻性队列、病例对照研究）及随机对照试验的事后分析。由两名研究者独立完成文献筛选、数据提取与文献质量评价，采用R语言进行Meta分析。本研究已在PROSPERO上注册（注册号：1144835）。共纳入11篇文献，涉及 7 255例患者。Meta分析结果显示irAE患者中，激素使用

未使用在总生存期（overall survival，OS）（HR=0.73，95% CI：0.45~1.18）及无进展生存期（progression-free survival，PFS）（HR=0.68，95% CI：0.00~98.01）方面差异均无统计学意义。在post-irAE OS（HR=0.95，95% CI：0.92~0.98）及post-irAE PFS（HR=0.96，95% CI：0.94~0.99）分析中，累积糖皮质激素剂量增加呈轻度保护性趋势。二线免疫抑制剂联合使用相比激素单用，在post-irAE OS（HR=1.40，95% CI：1.11~1.76）及post-irAE PFS（HR=1.32，95% CI：1.08~1.62）中显著增加疾病进展或死亡风险。敏感性分析显示，主要显著结果具有良好稳健性。当前证据提示，ICI相关irAE患者中，激素管理策略对生存结局的影响存在差异。累积激素剂量增加未表现为危险因素，二线免疫抑制剂联合使用可能增加生存风险。未来需进一步优化irAE管理策略，平衡免疫抑制治疗风险与抗肿瘤疗效，并通过前瞻性研究进一步验证。

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy

but their use is frequently complicated by immune-related adverse events (irAEs)

which often require management with corticosteroids or additional immunosuppressive agents. The prognostic impact of these therapeutic strategies in the setting of irAEs has not been systematically elucidated. This systematic review and meta-analysis aimed to evaluate the impact of corticosteroid (CS) and second-line immunosuppressant (IM) use on survival outcomes among patients who developed irAEs during ICI therapy. Following a preregistered protocol (PROSPERO CRD1144835)

we systematically searched PubMed

Embase

Web of Science

Cochrane Library

SinoMed

CNKI and Wanfang to identify studies published in the past 10 years (up to May 2025) reporting on the association between CS and IM use and survival outcomes in ICI-treated patients with irAEs. Two reviewers independently performed study selection

data extraction

and quality assessment. Meta-analyses were performed using R software. A total of 11 studies comprising 7 255 patients were included. Meta-analysis showed that CS use versus no use was not significantly associated with overall survival (OS) (HR=0.73

95% CI: 0.45-1.18) or progression-free survival (PFS) (HR=0.68

95% CI: 0.00-98.01). For post-irAE survival outcomes

higher cumulative CS dose (per 1 000 mg increment) was associated with a mild protective effect on post-irAE OS (HR=0.95

95% CI: 0.92-0.98) and post-irAE PFS (HR=0.96

95% CI: 0.94-0.99). In contrast to CS alone

IM use in combination with CS was associated with significantly increased risk of disease progression or death for post-irAE OS (HR=1.40

95% CI: 1.11-1.76) and post-irAE PFS (HR=1.32

95% CI: 1.08-1.62). Sensitivity analyses demonstrated good robustness of the main significant results. Current evidence suggests that CS and IM management strategies may differentially affect survival outcomes in patients with irAEs following ICI therapy. Increased cumulative CS dose is not associated with worse outcomes

whereas the addition of second-line IMs may increase the risk of adverse survival outcomes. Further prospective studies are warranted to optimize irAE management strategies and to balance the risks of immunosuppressive therapy with anticancer efficacy.

关键词

Keywords

references

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