When Checkpoint Inhibition Goes Off Target: A Rare Case of Pembrolizumab-Induced Acalculous Cholecystitis

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by improving survival across multiple malignancies by enhancing antitumor immune responses. However, increasing use of ICIs has been accompanied by a growing spectrum of immune-related adverse events (irAEs). Gastrointestinal irAEs most commonly include colitis and hepatitis, whereas biliary complications remain rare and poorly characterized. ICI-associated cholecystitis is an uncommon entity affecting patients treated with ICIs. It often presents as an acalculous disease and occurs months after therapy initiation. This report describes a case of a 64-year-old woman with lung adenocarcinoma receiving adjuvant pembrolizumab after surgical resection and chemotherapy who developed acute right upper quadrant pain and fatigue during her ninth treatment cycle. Imaging revealed significant gallbladder distension and wall thickening in the absence of gallstones, consistent with acute cholecystitis. Given high operative risk from concurrent ICI-induced adrenal insufficiency and absence of severe inflammatory findings, she was managed conservatively with intravenous fluids, antibiotics, and stress-dose corticosteroids, resulting in clinical improvement. Pembrolizumab was discontinued because of suspected immune-mediated toxicity, and she was discharged with plans for elective cholecystectomy and oncologic surveillance. This case highlights the importance of maintaining a high index of suspicion for biliary irAEs in patients receiving ICIs who present with abdominal symptoms and underscores the need for multidisciplinary management and further studies to guide optimal treatment strategies.