Lorlatinib-Induced Acute Pancreatitis Secondary to Severe Hypertriglyceridemia and Hyperglycemia: A Case Report

Abstract Background: Lorlatinib, a third-generation ALK tyrosine kinase inhibitor, is widely used in ALK-positive non–small cell lung cancer (NSCLC). While dyslipidemia and hyperglycemia are recognized adverse effects, acute pancreatitis secondary to these metabolic disturbances is rarely reported. Case Presentation: We describe the case of a 39-year-old male with stage IIIB ALK-positive lung adenocarcinoma who was initiated on lorlatinib therapy. Two months into treatment, he presented with acute abdominal pain and recurrent bilious vomiting. Laboratory investigations revealed severe hypertriglyceridemia (>9000 mg/dL), hyperglycemia (RBS 411 mg/dL), metabolic acidosis, and markedly elevated pancreatic enzymes. Imaging confirmed acute interstitial edematous pancreatitis with a CT severity index of 6. The patient was admitted to intensive care and managed with insulin infusion, fibrate therapy, heparin, bowel rest, and broad-spectrum antibiotics. Gradual improvement was observed, with triglycerides reduced to ~1100 mg/dL and resolution of abdominal pain and ileus. Lorlatinib was withheld at discharge for reassessment. Discussion: This case highlights the rare but significant risk of lorlatinib-induced acute pancreatitis secondary to severe hypertriglyceridemia and hyperglycemia. Although dyslipidemia is a well-recognized toxicity, progression to life-threatening pancreatitis remains uncommon. Routine monitoring of lipid and glucose profiles during therapy, particularly in the initial months, is critical to early detection and prevention. Conclusion: Prompt recognition of lorlatinib-induced metabolic derangements and a multidisciplinary management approach can lead to full recovery. Clinicians should maintain a high index of suspicion and ensure close metabolic monitoring in patients receiving lorlatinib. Keywords: Lorlatinib, ALK-positive lung cancer, pancreatitis, hypertriglyceridemia, hyperglycemia, targeted therapy, toxicity Introduction