A new classification of upper gastrointestinal toxicity induced by immunotherapy: from endoscopic and pathological insights to clinical management

Background

Immune checkpoint inhibitors (ICIs) have become the standard of care in several solid tumours. Thus the action of ICIs may lead to the development of inflammatory damage in nontumoral tissues, defined as immune-related adverse events (irAEs). Scanty data describe upper gastrointestinal tract toxicity.

Patients and methods

We conducted a monocentric retrospective study, enrolling patients with advanced cancer, who developed histology-proven immune-related oesophago-gastro-duodenitis, treated with at least one cycle of ICI between January 2016 and November 2022.

Results

We identified six patients with upper gastrointestinal irAEs: four affected by metastatic melanoma (three treated with nivolumab and one with nivolumab plus ipilimumab), one by unresectable cutaneous squamous cell carcinoma (treated with cemiplimab), and one by metastatic non-small-cell lung cancer (treated with pembrolizumab). Proton pump inhibitors and oral corticosteroids have been the mainstay of the management, and thus one patient had to receive intravenous methylprednisolone with hospitalisation, fasting, and parenteral nutrition. Based on the literature and our experience, we proposed a classification of ICI-induced upper gastrointestinal toxicity, with symptom and endoscopic sign grading. Each step of severity has been also correlated with a proposed diagnosis and clinical management.

Conclusions

During ICI treatment, upper gastrointestinal symptoms can be a red flag for developing severe oesophago-gastro-duodenal toxicity that can impact patients’ quality of life and therapeutic plan. We recommend carefully investigating these symptoms, choosing a multidisciplinary approach to decide if an oesophagogastroduodenoscopy with random biopsy is indicated. [18]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography might represent a promising complementary diagnostic tool. Steroids still represent the cornerstone of treatment, as for other irAEs.