S4729 Checkpoint Chaos: Immune Checkpoint Inhibitor Mediated Massive Hemorrhagic Gastritis

Introduction: Immune-checkpoint inhibitors (ICI), which block the cytotoxic T lymphocyte antigen 4 (CTLA-4) or programmed cell death protein 1 (PD-1) pathways, are being increasingly used for treatment of various malignancies. However, they pose a serious risk of gastrointestinal (GI) immune-related adverse events (irAEs), although upper GI manifestations are rare. We present a unique case of delayed-onset ICI-induced erosive duodenitis complicated by massive hemorrhagic and gastric outlet syndromes. Case Description/Methods: A 57-year-old man with history of metastatic renal cell carcinoma previously failed treatment with nivolumab and ipilumab, followed limited response to Pembrolizumab. Three months later, he presented with coffee ground emesis. Computed tomography (CT) chest showed increased lung metastasis with cavitation, concerning for hemoptysis and endoscopy was deferred. On day 3, he developed abdominal pain and vomiting with a rapid drop in hemoglobin from 14 to 10 g/dL. CT abdomen revealed gastric outlet obstruction due to superior mesenteric artery (SMA) syndrome. Endoscopy identified multiple duodenal ulcers. Biopsies showed erosive duodenitis with increased apoptotic bodies and extensive crypt dropout. A percutaneous endoscopic gastrostomy tube with jejunostomy tube (PEG-J) was placed for decompression and enteral nutrition. On day 21, he developed massive upper GI bleeding from PEG-J site requiring massive transfusion protocol. A bleeding duodenal ulcer was identified and treated with bipolar therapy. High dose steroids were started, and ICI therapy was discontinued. Discussion: This case underscores 3 clinical aspects of ICI toxicity. First, GI irAEs may well present beyond the typical 3–6-week window after ICI initiation, necessitating vigilance throughout the treatment course. Second, histopathologic features like crypt dropout and apoptotic bodies highlight the extent of mucosal injury, suggesting a pathophysiological basis for hemorrhage through mucosal friability. While apoptotic bodies are a nonspecific finding also seen in viral, drug-induced, or autoimmune processes, their presence in this clinical context strongly supports immune-mediated injury. Third, the presence of superior mesenteric artery syndrome exacerbated the clinical course by impairing nutrition and delaying mucosal healing. Early PEG-J placement was key for both decompression and nutritional support. Therefore, prompt recognition, biopsy, and multidisciplinary management are critical to balancing immunosuppression with oncologic control.