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Colli Cruz C, Moura Nascimento Santos MJ, Wali S, Varatharajalu K, Thomas A, Wang Y. Gastrointestinal toxicities associated with immune checkpoint inhibitors therapy: risks and management. Immunotherapy 2025; 17:293-303. [PMID: 40055892 PMCID: PMC12013428 DOI: 10.1080/1750743x.2025.2473305] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 02/25/2025] [Indexed: 04/22/2025] Open
Abstract
Immune checkpoint inhibitors (ICIs) have greatly improved cancer treatment by boosting the immune system's ability to target tumors. However, they can also cause serious side effects, particularly in the digestive system. These include immune-related diarrhea, inflammation of the intestines and, less commonly, inflammation of the stomach or esophagus. This review underscores the importance of early detection, accurate diagnosis, and timely treatment to improve patient outcomes. It also highlights the need for further research to develop strategies to reduce gastrointestinal toxicities and enhance the overall effectiveness of ICIs in cancer therapy.
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Affiliation(s)
- Carolina Colli Cruz
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Sharada Wali
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Krishnavathana Varatharajalu
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Anusha Thomas
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yinghong Wang
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Su F, Fan WX, Zhang Y, Zhang XL, Du YY, Li WL, Hu WQ, Zhao J. A systematic review of gastritis as an immune-related adverse event in clinical interventions. Hum Vaccin Immunother 2024; 20:2408852. [PMID: 39434209 PMCID: PMC11497991 DOI: 10.1080/21645515.2024.2408852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 09/10/2024] [Accepted: 09/23/2024] [Indexed: 10/23/2024] Open
Abstract
Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment, and the associated immune-related adverse events (irAEs) have garnered significant attention, yet reports on associated immune related gastritis are limited. The diagnosis of immune related gastritis remains predominantly exclusionary, meanwhile its management diverges significantly from that of conventional gastritis. Current guidelines lack standardized grading criteria, and substantial data from large-scale, tertiary clinical studies are absent, therefore we conducted a systematic review of Medline, Web of Science, and Embase databases, identifying 31 articles from 2017 to December 31, 2023, involving 258 patients. Clinical manifestations included epigastric pain (53.1%), mucosal erythema (56.1%), and lymphocyte infiltration (48.6%). Corticosteroid therapy was common (94.7%), with 86.7% experiencing post-treatment improvement. 80% of patients can be diagnosed through endoscopy and pathology, while the remaining 20% may require PET-CT. Hormonal therapy is favored but diverges from standard management. Accurate diagnosis is crucial in managing immune related gastritis effectively.
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Affiliation(s)
- Fei Su
- Department of Graduate School, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Oncology, Changzhi People’s Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China
| | - Wen-Xuan Fan
- Department of Graduate School, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Oncology, Changzhi People’s Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China
| | - Yan Zhang
- Department of Oncology, Changzhi People’s Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China
- Department of Graduate School, Changzhi Medical College, Changzhi, Shanxi, China
| | - Xiao-Ling Zhang
- Department of Oncology, Changzhi People’s Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China
| | - Yun-Yi Du
- Department of Oncology, Changzhi People’s Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China
| | - Wei-Ling Li
- Department of Oncology, Changzhi People’s Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China
- Department of Graduate School, Changzhi Medical College, Changzhi, Shanxi, China
| | - Wen-Qing Hu
- Department of Gastrointestinal Surgery, Changzhi People’s Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China
| | - Jun Zhao
- Department of Oncology, Changzhi People’s Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China
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Shatila M, Zhang HC, Shirwaikar Thomas A, Machado AP, Naz S, Mittal N, Catinis C, Varatharajalu K, Colli Cruz C, Lu E, Wu D, Brahmer JR, Carbonnel F, Hanauer SB, Lashner B, Schneider B, Thompson JA, Obeid M, Farris DP, Wang Y. Systematic review of immune checkpoint inhibitor-related gastrointestinal, hepatobiliary, and pancreatic adverse events. J Immunother Cancer 2024; 12:e009742. [PMID: 39542654 PMCID: PMC11575294 DOI: 10.1136/jitc-2024-009742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/23/2024] [Indexed: 11/17/2024] Open
Abstract
Gastrointestinal immune-related adverse events (GI irAEs) are common manifestations of immune checkpoint inhibitor (ICI) toxicity. We present a comprehensive systematic review of the incidence, management, and clinical course of irAEs across the entire GI system, including the luminal GI tract, liver, and pancreas. MEDLINE, Embase, Web of Science Core Collection, and Cochrane Library were used to conduct this review. All studies pertaining to GI irAEs were included. Both abstracts and full manuscripts were eligible if they included human subjects and were written in the English language. Articles not available in English, animal studies, or research not specific to GI toxicity of immunotherapy were excluded. We excluded certain article types depending on whether stronger evidence was available in the literature for a specific toxicity, for example, if prospective studies were available on a topic, retrospective studies and case reports were excluded. We extracted a final 166 articles for our review and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for data reporting. Risk of bias tools were not used to evaluate the extracted studies given the narrative nature of this manuscript, but each study was critically appraised by the manuscript writer. We detail the incidence, presentation, evaluation, management, and outcomes of the various GI toxicities that may arise with ICI therapy. Specifically, we discuss the characteristics of upper GI toxicity (esophagitis and gastroenteritis), lower GI toxicity (colitis), hepatobiliary inflammation, pancreatitis, and rarer forms of GI toxicity. We hope this review serves as a useful and accessible clinical tool that helps physicians familiarize themselves with the nuances of gastrointestinal/hepatic/pancreatic ICI toxicity diagnosis and management.
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Affiliation(s)
- Malek Shatila
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Hao Chi Zhang
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Anusha Shirwaikar Thomas
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Antonio Pizuorno Machado
- Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Sidra Naz
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Nitish Mittal
- Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Christine Catinis
- Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Krishnavathana Varatharajalu
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Carolina Colli Cruz
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Eric Lu
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Deanna Wu
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Julie R Brahmer
- Department of Thoracic Medical Oncology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Franck Carbonnel
- Department of Gastroenterology, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Stephen B Hanauer
- Department of Gastroenterology, Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA
| | - Bret Lashner
- Center for Inflammatory Bowel Disease, Cleveland Clinic, Cleveland, Ohio, USA
| | - Bryan Schneider
- Department of Thoracic Medical Oncology, University of Michigan, Ann Arbor, Michigan, UK
| | - John A Thompson
- Department of Medicine, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, USA
| | - Michel Obeid
- Department of Medicine, Service of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - David P Farris
- Research Medical Library, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Yinghong Wang
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Lin J, Lin ZQ, Zheng SC, Chen Y. Immune checkpoint inhibitor-associated gastritis: Patterns and management. World J Gastroenterol 2024; 30:1941-1948. [PMID: 38681126 PMCID: PMC11045486 DOI: 10.3748/wjg.v30.i14.1941] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 02/23/2024] [Accepted: 03/28/2024] [Indexed: 04/12/2024] Open
Abstract
Immune checkpoint inhibitors (ICIs) are widely used due to their effectiveness in treating various tumors. Immune-related adverse events (irAEs) are defined as adverse effects resulting from ICI treatment. Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects, such as diarrhea and colitis, which may lead to the cessation of ICIs. Although irAE gastritis is rarely reported, it may lead to serious complications such as gastrorrhagia. Furthermore, irAE gastritis is often difficult to identify early due to its diverse symptoms. Although steroid hormones and immunosuppressants are commonly used to reverse irAEs, the best regimen and dosage for irAE gastritis remains uncertain. In addition, the risk of recurrence of irAE gastritis after the reuse of ICIs should be considered. In this editorial, strategies such as early identification, pathological diagnosis, management interventions, and immunotherapy rechallenge are discussed to enable clinicians to better manage irAE gastritis and improve the prognosis of these patients.
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Affiliation(s)
- Jing Lin
- Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350000, Fujian Province, China
| | - Zhong-Qiao Lin
- Phase I Clinical Trial Ward, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350000, Fujian Province, China
| | - Shi-Cheng Zheng
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350000, Fujian Province, China
| | - Yu Chen
- Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350000, Fujian Province, China
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Mok K, Wu C, Chan S, Wong G, Wong VWS, Ma B, Lui R. Clinical Management of Gastrointestinal and Liver Toxicities of Immune Checkpoint Inhibitors. Clin Colorectal Cancer 2024; 23:4-13. [PMID: 38172003 DOI: 10.1016/j.clcc.2023.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/11/2023] [Accepted: 12/12/2023] [Indexed: 01/05/2024]
Abstract
Immune checkpoint inhibitors have transformed the treatment paradigm for various types of cancer. Nonetheless, with the utilization of these groundbreaking treatments, immune-related adverse events (irAEs) are increasingly encountered. Colonic and hepatic involvement are among the most frequently encountered irAEs. Drug-induced side effects, infectious causes, and tumor-related symptoms are the key differentials for irAE complications. Potential risk factors for the development of irAEs include combination use of immune checkpoint inhibitors, past development of irAEs with other immunotherapy treatments, certain concomitant drugs, and a pre-existing personal or family history of autoimmune illness such as inflammatory bowel disease. The importance of early recognition, timely and proper management cannot be understated, as there are profound clinical implications on the overall cancer treatment plan and prognosis once these adverse events occur. Herein, we cover the clinical management of the well-established gastrointestinal irAEs of enterocolitis and hepatitis, and also provide an overview of several other emerging entities.
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Affiliation(s)
- Kevin Mok
- Department of Clinical Oncology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Claudia Wu
- Division of Gastroenterology and Hepatology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China; Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Stephen Chan
- State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Sir YK Pao Centre for Cancer, Hong Kong Cancer Institute, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - Grace Wong
- Division of Gastroenterology and Hepatology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China; Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Vincent Wai-Sun Wong
- Division of Gastroenterology and Hepatology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China; Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Brigette Ma
- Department of Clinical Oncology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China; Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Rashid Lui
- Department of Clinical Oncology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China; Division of Gastroenterology and Hepatology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China; Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong SAR, China.
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