S3942 Zolbetuximab-Induced Colitis Leading to Colonic Perforation: A Call for Researching a Novel Drug

Introduction: Zolbetuximab is a novel chimeric monoclonal antibody that is used in patients with advanced gastric or gastro-esophageal junction (G/GEJ) adenocarcinoma. It targets Claudin 18.2 is a protein that is often overexpressed in gastric and GEJ cancers. Acute diarrhea is a recognized adverse reaction associated with zolbetuximab. We present the first documented case of a woman with poorly differentiated gastric adenocarcinoma that developed acute colitis complicated by perforation after initiation of zolbetuximab. Case Description/Methods: An 85-year-old woman with history of hypertension, atrial fibrillation, mitral regurgitation, congenital hypertriglyceridemia, osteoporosis, and moderately to poorly differentiated adenocarcinoma of the stomach diagnosed 4 months prior to admission. She was on standard chemotherapy “FOLFOX” and developed acute profuse watery diarrhea after addition of zolbetuximab. She reported 12-15 bowel movements daily after starting Zolbetuximab. Stool studies for gastrointestinal infections were negative. Abdominal computed tomography (CT) was notable for contained rectal wall perforation, pneumatosis intestinalis in the transverse colon, and hyperemic appearance of small-bowel loops, concerning for enteritis. The diarrhea persisted through scheduled Lomotil, Loperamide, and cholestyramine. A repeat abdominal CT demonstrating spontaneous resolution of the rectal perforation and interval decrease of the transverse colon pneumatosis. Sigmoidoscopy with water immersion was notable for an ulcer located in the transverse colon and severe localized inflammation of the sigmoid colon and diverticulosis with biopsy demonstrating acute inflammation, negative for cytomegalovirus. Her symptoms gradually improved with conservative management. Discussion: The most common adverse reactions in patients on zolbetuximab with chemotherapy are nausea, vomiting, fatigue, and diarrhea. Management of aolbetuximab-induced acute diarrhea involves supportive care, including assessment of severity, correction of fluid and electrolyte imbalances, and antidiarrheal agents as clinically indicated. Given the onset of symptoms shortly after initiation of zolbetuximab without evidence of infection, this case represents zolbetuximab-induced colitis complicated with colonic perforation which is not a well-documented adverse reaction. This is a potentially serious complication to a novel agent which may require further evaluation in phase IV clinical trials and monitoring in clinical practice.