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多国癌症支持治疗协会(MASCC)2020 年关于检查点抑制剂引起的严重胃肠道和肝脏毒性管理的临床实践建议。

Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of severe gastrointestinal and hepatic toxicities from checkpoint inhibitors.

机构信息

Massachusetts General Hospital, Boston, MA, USA.

Harvard Medical School, Boston, MA, USA.

出版信息

Support Care Cancer. 2020 Dec;28(12):6129-6143. doi: 10.1007/s00520-020-05707-3. Epub 2020 Aug 27.


DOI:10.1007/s00520-020-05707-3
PMID:32856210
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8507388/
Abstract

Immune-related adverse events (IrAEs) affecting the gastrointestinal (GI) tract and liver are among the most frequent and most severe inflammatory toxicities from contemporary immunotherapy. Inflammation of the colon and or small intestines (entero)colitis is the single most common GI IrAE and is an important cause of delay of discontinuation of immunotherapy. The severity of these GI IrAEs can range from manageable with symptomatic treatment alone to life-threatening complications, including perforation and liver failure. The frequency and severity of GI IrAEs is dependent on the specific immunotherapy given, with cytotoxic T lymphocyte antigen (CTLA)-4 blockade more likely to induce severe GI IrAEs than blockade of either programmed cell death protein 1 (PD-1) or PD-1 ligand (PD-L1), and combination therapy showing the highest rate of GI IrAEs, particularly in the liver. To date, we have minimal prospective data on the appropriate diagnosis and management of GI IrAEs, and recommendations are based largely on retrospective data and expert opinion. Although clinical diagnoses of GI IrAEs are common, biopsy is the gold standard for diagnosis of both immunotherapy-induced enterocolitis and hepatitis and can play an important role in excluding competing, though less common, diagnoses and ensuring optimal management. GI IrAEs typically respond to high-dose corticosteroids, though a significant fraction of patients requires secondary immune suppression. For colitis, both TNF-α blockade with infliximab and integrin inhibition with vedolizumab have proved highly effective in corticosteroid-refractory cases. Detailed guidelines have been published for the management of low-grade GI IrAEs. In the setting of more severe toxicities, involvement of a GI specialist is generally recommended. The purpose of this review is to survey the available literature and provide management recommendations focused on the GI specialist.

摘要

免疫相关不良事件(IrAEs)影响胃肠道(GI)和肝脏,是当代免疫治疗中最常见和最严重的炎症毒性之一。结肠和/或小肠炎症(结肠炎)是最常见的 GI IrAE,也是延迟免疫治疗停药的重要原因。这些 GI IrAEs 的严重程度可从仅用对症治疗即可控制到危及生命的并发症,包括穿孔和肝功能衰竭。这些 GI IrAEs 的频率和严重程度取决于具体的免疫治疗药物,细胞毒性 T 淋巴细胞抗原(CTLA)-4 阻断剂比程序性细胞死亡蛋白 1(PD-1)或 PD-1 配体(PD-L1)阻断剂更有可能引起严重的 GI IrAEs,联合治疗显示出最高的 GI IrAEs 发生率,特别是在肝脏。迄今为止,我们对 GI IrAEs 的适当诊断和管理仅有很少的前瞻性数据,建议主要基于回顾性数据和专家意见。虽然 GI IrAEs 的临床诊断很常见,但活检是免疫治疗诱导性结肠炎和肝炎的金标准,在排除竞争较少但更常见的诊断和确保最佳管理方面发挥着重要作用。GI IrAEs 通常对高剂量皮质类固醇有反应,但相当一部分患者需要二级免疫抑制。对于结肠炎,英夫利昔单抗的 TNF-α 阻断和 vedolizumab 的整合素抑制在皮质类固醇难治性病例中均被证明非常有效。已经为低级别 GI IrAEs 的管理发布了详细指南。在更严重毒性的情况下,通常建议由 GI 专家参与。本综述的目的是调查现有文献并提供以 GI 专家为重点的管理建议。

相似文献

[1]
Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of severe gastrointestinal and hepatic toxicities from checkpoint inhibitors.

Support Care Cancer. 2020-12

[2]
Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune-related adverse events: pulmonary toxicity.

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[3]
Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune checkpoint inhibitor endocrinopathies and the role of advanced practice providers in the management of immune-mediated toxicities.

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[4]
Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune-mediated cardiovascular, rheumatic, and renal toxicities from checkpoint inhibitors.

Support Care Cancer. 2020-12

[5]
Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of severe dermatological toxicities from checkpoint inhibitors.

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[6]
The determinants of very severe immune-related adverse events associated with immune checkpoint inhibitors: A prospective study of the French REISAMIC registry.

Eur J Cancer. 2021-11

[7]
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[8]
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[9]
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J Hepatol. 2018-2-8

[10]
Prophylactic IL-23 blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy.

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引用本文的文献

[1]
High Grade Hepatotoxicity From Dual Checkpoint Inhibitors Is More Common in Hepatocellular Carcinoma Than Other Cancers.

Liver Int. 2025-9

[2]
Function of F-FDG PET/CT radiomics in the detection of checkpoint inhibitor-induced liver injury (CHILI).

EJNMMI Rep. 2025-8-4

[3]
British Society of Gastroenterology practice guidance on the management of acute and chronic gastrointestinal symptoms and complications as a result of treatment for cancer.

Gut. 2025-6-6

[4]
Hepatotoxicity in Cancer Immunotherapy: Diagnosis, Management, and Future Perspectives.

Cancers (Basel). 2024-12-29

[5]
Developing alert thresholds and self-management advice for people receiving immune checkpoint inhibitors: a Multinational Association for Supportive Care in Cancer modified Delphi survey.

Support Care Cancer. 2025-1-7

[6]
Delayed-Onset Immune-Related Colitis Following Pancreaticoduodenectomy in Patients With Gastric Cancer and Pancreatic Invasion Treated With Immune Checkpoint Inhibitors.

Cureus. 2024-9-2

[7]
Hepatobiliary complications of immune checkpoint inhibitors in cancer.

Explor Target Antitumor Ther. 2024

[8]
Reactive cutaneous capillary endothelial proliferation following camrelizumab monotherapy or combination therapy for multi-cancers: a large-scale pooled analysis of 10 studies in China.

Ther Adv Med Oncol. 2024-4-10

[9]
Psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors.

An Bras Dermatol. 2024

[10]
Immune checkpoint inhibitors and risk of immune-mediated adverse events: a cohort study comparing extended versus standard interval administration.

Clin Exp Med. 2024-2-22

本文引用的文献

[1]
Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis.

J Immunother Cancer. 2020-5

[2]
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J Immunother Cancer. 2019-11-7

[3]
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Oncologist. 2019-11-6

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Histopathology. 2019-11-13

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Trends Immunol. 2019-4-30

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J Immunother Cancer. 2019-5-3

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Case Rep Oncol. 2019-2-8

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Prophylactic TNF blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy.

Nature. 2019-5-1

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Early introduction of selective immunosuppressive therapy associated with favorable clinical outcomes in patients with immune checkpoint inhibitor-induced colitis.

J Immunother Cancer. 2019-4-2

[10]
Toxicities with Immune Checkpoint Inhibitors: Emerging Priorities From Disproportionality Analysis of the FDA Adverse Event Reporting System.

Target Oncol. 2019-4

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