S3406 Early-Onset Pancreatitis After a Single Dose of Combination Immune Checkpoint Inhibitor Therapy

Introduction: Immune checkpoint inhibitors (ICIs) like nivolumab and ipilimumab unleash T-cell antitumor activity but can cause immune-related adverse events. Gastrointestinal toxicities particularly colitis and hepatitis are common, whereas pancreatitis is rare (<1%) and usually appears later, making it easy to miss. This is a rare case of pancreatitis shortly after a single cycle of nivolumab and ipilimumab. Case Description/Methods: A 75-year-old woman with a history of left nephrectomy for renal cell carcinoma, prior lung cancer radiation, and an active pelvic malignancy presented with 3 days of worsening upper abdominal pain radiating to the back, with nausea and vomiting. She had completed pelvic radiation and received her first dose of combined nivolumab and ipilimumab 1 week prior. She reported poor tolerance of food, fluids, and medications, along with fatigue and low-grade fever. On exam, she was hemodynamically stable but tender in the upper quadrants without peritoneal signs. Labs showed a drop in hemoglobin from 13.9 to 9.0 g/dL, normal white blood cell and platelet counts, mildly elevated lipase at 97 U/L, normal liver function tests, hypomagnesemia, hypophosphatemia, and triglycerides of 205 mg/dL. Computed tomography abdomen/pelvis showed chronic pancreatitis with possible mild acute inflammation, prior nephrectomy, and a suspicious sacral lesion. She denied alcohol use, gallstones, prior pancreatitis, or recent procedures. Given the timing after ICI initiation and exclusion of other causes, immune-related pancreatitis was suspected. She received intravenous fluids, antiemetics, and electrolyte replacement without corticosteroids, and was discharged after symptom improvement. Discussion: ICIs can cause rare immune-related pancreatitis (<1%), usually later in treatment, but this patient developed it just 1 week after her first dose. Nonspecific symptoms (abdominal pain, nausea, vomiting), mild lipase elevation, and imaging suggesting acute-on-chronic pancreatitis, along with exclusion of alcohol, gallstones, hypertriglyceridemia, and procedures, pointed to an immune cause. Though the mechanism is unclear, heightened T-cell activity from combination ICI likely drove early pancreatic inflammation. With limited guidelines for ICI-related pancreatitis, mild cases are managed supportively (intravenous fluids, antiemetics, electrolytes) without steroids, as in this case. Clinicians should consider pancreatitis even after a single ICI dose and rely on clinical judgment for timely diagnosis and care.