Omar Alkasabrah, MD¹, Abdullah Hafeez, MD¹, Dhruvi Sanikommu, MD¹, Amanda Lussier, MD¹, Sameeha Ibrahim, MD², Jatin Thukral, MD¹, Sooraj Gopu, MD¹, Omar Jamil, MD³
1Landmark Medical Center, Woonsocket, RI; 2Jordan University of Science and Technology, Al Ramtha, Irbid, Jordan; 3University of Chicago, Chicago, IL

Introduction: Immune checkpoint inhibitors (ICIs) like pembrolizumab, a monoclonal antibody targeting the programmed death-1 (PD-1) receptor, have revolutionized cancer therapy, particularly for non-small cell lung cancer. While immune-related adverse events (irAEs) commonly affect the lower gastrointestinal (GI) tract, upper GI involvement remains rare. This case highlights pembrolizumab-induced hemorrhagic gastritis, an uncommon but serious irAE.

Case Description/

Methods: A 55-year-old woman with lung adenocarcinoma underwent lobectomy followed by pembrolizumab maintenance therapy. She presented with persistent nausea, vomiting, hematemesis, and abdominal pain. On admission, she was hemodynamically stable. Labs revealed hemoglobin of 12.1 g/dL and lipase of 150 U/L; other parameters were unremarkable. CT imaging demonstrated gastric wall thickening without obstruction. Esophagogastroduodenoscopy (EGD) revealed diffuse erosive, ulcerative, and hemorrhagic gastritis with friable, oozing mucosa in the fundus and antrum. Gastric biopsies confirmed immune checkpoint inhibitor-induced gastritis. Initial management with IV pantoprazole and antiemetics provided transient relief. However, her symptoms recurred, prompting readmission. High-dose intravenous steroids were initiated, resulting in significant clinical improvement. She was discharged on a high-dose oral prednisone taper. Pembrolizumab was discontinued, and follow-up showed complete symptom resolution.

Discussion: ICIs enhance antitumor immunity by blocking inhibitory pathways such as PD-1 but can induce irAEs due to off-target immune activation. While colitis is a well-recognized GI irAE, upper GI manifestations like hemorrhagic gastritis are rare but potentially life-threatening. This case emphasizes the need for clinical vigilance when patients on ICIs present with upper GI symptoms. The pathophysiology is thought to involve T-cell-mediated mucosal injury from loss of peripheral tolerance. Endoscopic and histologic evaluation is essential for diagnosis. Management includes prompt initiation of corticosteroids and discontinuation of the offending agent in cases of severe toxicity. This case shows the importance of recognizing upper GI irAEs, which, though uncommon, warrant early intervention to prevent serious outcomes. Endoscopic evaluation should be strongly considered in symptomatic patients receiving ICI therapy. Further research is needed to guide optimal management of upper GI toxicities in this population.

Disclosures:
Omar Alkasabrah indicated no relevant financial relationships.
Abdullah Hafeez indicated no relevant financial relationships.
Dhruvi Sanikommu indicated no relevant financial relationships.
Amanda Lussier indicated no relevant financial relationships.
Sameeha Ibrahim indicated no relevant financial relationships.
Jatin Thukral indicated no relevant financial relationships.
Sooraj Gopu indicated no relevant financial relationships.
Omar Jamil indicated no relevant financial relationships.

Omar Alkasabrah, MD¹, Abdullah Hafeez, MD¹, Dhruvi Sanikommu, MD¹, Amanda Lussier, MD¹, Sameeha Ibrahim, MD², Jatin Thukral, MD¹, Sooraj Gopu, MD¹, Omar Jamil, MD³. P5242 - Hemorrhagic Gastritis as an Immune-Related Adverse Event of Pembrolizumab in a Patient With Lung Adenocarcinoma, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.