The Development of Persistent Gastrointestinal Symptoms in Patients With Melanoma Who Have Had an Immune Checkpoint Inhibitor-Related Gastrointestinal Toxicity

• Published in: Clinical and translational gastroenterology 2024-08, Vol.15 (8), p.e00746
• Main Authors: Varma, Sanskriti, Sullivan, Keri, DiCarlo, Jamie, Coromilas, Alexandra, Staller, Kyle, Dougan, Michael
• Format: Article
• Language: English
• Subjects: Abdomen; Constipation; Cytotoxicity; Diarrhea; Endoscopy; Fecal incontinence; Functional GI Disorders; Gastroenteritis; Immunotherapy; Inflammation; Inflammatory bowel disease; Irritable bowel syndrome; Medical records; Melanoma; Nausea; Toxicity; Vomiting
• ISSN: 2155-384X; 2155-384X
• DOI: 10.14309/ctg.0000000000000746

Immune-related adverse events (irAE) secondary to immune checkpoint inhibitors (ICI) have gastrointestinal (GI) manifestations, including gastritis, enteritis, and/or colitis. The long-term sequelae of ICI-associated GI toxicities (GI-irAE), particularly the development of disorders of gut-brain interaction, are not well known. We characterized the incidence of persistent GI symptoms after GI-irAE. This is a retrospective study of adults with melanoma treated with ICI and diagnosed with GI-irAE at our institution from 2013 to 2021. All patients had endoscopic and histologic evidence of GI-irAE. The primary outcome was incidence of persistent GI symptoms (diarrhea, abdominal pain, bloating, constipation, fecal incontinence, nausea, vomiting) after resolution of GI-irAE. Hazard ratios evaluated the association between parameters and time to persistent GI symptoms. One hundred four patients with melanoma (90% stage IV disease) and GI-irAE met inclusion criteria. Thirty-four percent received anti-cytotoxic T lymphocyte-associated protein-4 therapy, 33% anti-programmed death-1, and 34% dual therapy. Patients were treated for GI-irAE for an average of 9 ± 6 weeks. Twenty-eight (27%) patients developed persistent GI symptoms 1.6 ± 0.8 years after GI-irAE. The most common symptom was constipation (17%), followed by bloating (8%) and diarrhea (5%). Over 453 person-years, the incident rate was 6.2% per 100 person-years. Use of cytotoxic T lymphocyte-associated protein-4 single or dual therapy was associated with a 3.51× risk of persistent GI symptoms (95% confidence interval 1.20-10.23). In this cohort of melanoma patients who experienced GI-irAE, 26% developed persistent GI symptoms, most frequently constipation. Future studies should characterize the GI sequelae after GI-irAE, which may shed light on disorders of gut-brain interaction pathogenesis and improve the lives of cancer survivors.