[Gastrointestinal complications of the new immune checkpoint inhibitor therapies]
Julian Götze1, Michael Bitzer1, Nisar Peter Malek1
1Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Dept. für Innere Medizin, Universitätsklinik Tübingen.
Abstract:
In recent years, immune checkpoint inhibitors (ICPI) have become established as an integral part of drug tumor therapy. They belong to a group of monoclonal antibodies that promote anti-cancer cell immune response. Inhibitory signaling pathways are interrupted by binding to CTLA-4 and PD-1 or PD-L1, which increases the activity of cytotoxic T lymphocytes and reduces the immunological tolerance to tumor cells.Diarrhea - a symptom of enterocolitis - is the most common side effect of ICPI therapy after dermatological phenomena. A combined CTLA-4 and PD-1 blockade may affect up to 44 % of patients. The symptoms of ICPI-associated colitis are similar to the clinical appearance of inflammatory bowel disease.The treatment of affected patients should follow a standardized approach. Both the European and American Oncology Societies offer specific recommendations for the diagnosis and treatment of ICPI-associated adverse reactions. Rapid immunosuppressant treatments, to include steroids and biologics, are necessary to reduce morbidity once differential diagnoses are excluded. It may then be possible to subsequently resume ICPI therapy.Immune-mediated hepatitis is a potential side effect which occurs about 6 to 14 weeks after initiation of therapy. It is usually asymptomatic and characterized by an increase in serum transaminases. Lipasemia, without clinical signs of acute pancreatitis, is a common laboratory finding, which usually has no therapeutic consequence.
Insights
Immune checkpoint inhibitors (ICPI) enhance anti-cancer immunity but can cause side effects like colitis and hepatitis. Prompt diagnosis and immunosuppressive treatment are crucial for managing these adverse reactions and potentially resuming therapy.
Area of Science:
- Oncology
- Immunology
- Gastroenterology
Background:
- Immune checkpoint inhibitors (ICPI) are monoclonal antibodies enhancing anti-cancer immune responses by blocking CTLA-4, PD-1, or PD-L1.
- ICPI therapy can lead to immune-mediated adverse events, notably enterocolitis (diarrhea) and hepatitis.
Purpose of the Study:
- To review the common side effects of ICPI therapy, focusing on colitis and hepatitis.
- To outline current recommendations for the diagnosis and management of ICPI-associated adverse reactions.
Main Methods:
- Review of current literature and clinical guidelines regarding ICPI therapy and its side effects.
- Analysis of the incidence, clinical presentation, and management strategies for ICPI-associated colitis and hepatitis.
Main Results:
- Diarrhea, a symptom of enterocolitis, is the most frequent ICPI side effect, affecting up to 44% with combined blockade.
- Immune-mediated hepatitis typically occurs 6-14 weeks post-therapy, often asymptomatic with elevated transaminases.
- Standardized treatment approaches involving steroids and biologics are recommended for managing ICPI-associated colitis.
Conclusions:
- ICPI-associated colitis and hepatitis require prompt recognition and management following established guidelines.
- Early immunosuppressive treatment is essential to mitigate morbidity and allow for potential re-initiation of ICPI therapy.
- Lipasemia is a common laboratory finding in ICPI-associated hepatitis but usually requires no specific intervention.
Related Concept Videos
Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
Chronic Bowel Disorders: Introduction
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
Other Disorders of Digestive System


