ICI-related gastrointestinal events on the rise

 Gastrointestinal (GI) toxicity from immune checkpoint inhibitors (ICIs) is a growing issue associated with the increasing use of immunotherapies in oncology and must be adequately investigated and managed, heard the Irish Society of Gastroenterology Winter Meeting 2024.

Prof Derek Power, Consultant Medical Oncologist, Cork University Hospital, and national principal investigator on several clinical trials in GI cancers and melanoma at Cancer Trials Ireland, said ICIs have been “practice changing” in oncology. ICIs have become the standard of care in several cancers and have significantly improved survival rates in melanoma.

ICIs enhance anti-tumour T-cell activity, also leading to a systemic loss of tolerance with resulting immune-related adverse events (irAEs). Thus, it is essential to improve understanding of these events, he told the meeting.

Gastrointestinal irAEs such as immune-related enterocolitis are among the most common and severe and there are still no validated biomarkers for irAEs, Prof Power said.

This type of colitis is the cause of most ICI-associated diarrhoea (first rule-out coeliac disease, microscopic colitis, and complications from malignancy), and is more common with CTLA-4 blockade than with PD-1 blockade (each causing a distinct subtype), with the severity ranging from indolent to life-threatening, he explained. While it is often isolated, it can involve the GI tract from stomach to the rectum.

A flexible sigmoidoscopy is usually sufficient for diagnosis. Early endoscopy can be useful for risk stratification and treatment guidance, Prof Power reported. Treatment is usually IV methylprednisolone (inpatients), and prednisone, with careful consideration to steroid treatment strength and duration due to the impact on ICI effectiveness and longer-term side-effects, he said. Antibodies to TNFa (eg, infliximab) are highly effective in treatment-resistant ICI colitis, as are other secondary suppression agents like vedolizumab, he added. Microscopic colitis from immunotherapy can respond well to budesonide.

Prof Power also discussed more refractory cases, their treatment, and the various guidelines, algorithms, and the evolving paradigm of management. Looking to the future, he noted ongoing research on the role of the microbiome and the use of faecal microbiota transplantation.

Discussing treating inflammatory bowel disease patients with ICIs, Prof Power said that their disease should not be considered a contraindication, but the patient’s gastroenterologist should be involved from the beginning. These patients should be carefully monitored with a high level of suspicion for any adverse events.