Acute Pancreatitis Secondary to Pembrolizumab-Induced Hypertriglyceridemia: First Clinical Experience

Introduction: Pembrolizumab is a programmed cell death receptor-1 (PD-1) inhibitor that has revolutionized therapeutics in several advanced cancers. A plethora of immune-related adverse events have also been reported, including pneumonitis, colitis, hepatitis, and autoimmune diabetes. Pembrolizumab-induced hypertriglyceridemia (HTG) has also been reported, but acute pancreatitis secondary to this complication remains an unusual entity. To our knowledge, our patient is the first case of acute pancreatitis with pembrolizumab-related severe HTG as the probable etiological factor. Case Description/Methods: A 39-year-old woman with stage IVB non-small-cell lung cancer presented with progressive abdominal pain and nausea, 14 days after receiving a pembrolizumab-based chemotherapy cycle. Her lipid profile was normal before pembrolizumab initiation 4 months ago. Laboratory studies revealed serum lipase 12562 IU/L and triglyceride 16901 mg/dL, with significantly elevated HbA1c and deranged liver and renal function test results (Table). As per the Revised Atlanta Classification, the patient was diagnosed with acute pancreatitis as she fulfilled all 3 criteria. After careful exclusion of alternative etiologies, pembrolizumab-induced HTG was considered as the probable cause. She was then transferred to the ICU for treatment with fluid replacement and insulin infusion. However, HTG did not respond to conservative treatment with insulin infusion. Subsequently, she received 2 cycles of therapeutic plasma exchange. The patient recovered well with no complications. Discussion: The exact pathogenesis of pembrolizumab-induced HTG remains unclear. However, the deficiency or autoantibodies targeting GP1HBP1 may have a role by halting lipoprotein lipase (LPL) to reach capillary lumen. It causes low LPL levels and deranged intravascular degradation of triglycerides, culminating in HTG. This article has pertinent clinical implications due to the widespread use of immune checkpoint inhibitors. Community awareness regarding different presentations of such rare adverse events is imperative for clinical management in order to avoid morbidity and mortality. HTG can be treated with insulin infusion or therapeutic plasma exchange. Monitoring of serum triglyceride levels at baseline, during, and after pembrolizumab therapy can be considered, particularly in patients with diabetes and lipid disorders. Therefore, clinicians should remain vigilant for acute pancreatitis as it can be a life-threatening adverse event of immune-checkpoint inhibitors. Table 1. - Laboratory data of the patient at the initial presentation showing remarkably deranged results Laboratory parameter Patient value Reference range Lipase 12562 23-300 IU/L Triglycerides 16901 10-150 mg/dL Total cholesterol 1387 < 200 mg/dL Low-density lipoprotein 1016 50-100 mg/dL Alanine aminotransferase 385 0-34 IU/L Aspartate aminotransferase 243 15-46 IU/L Alkaline phosphatase 618 45-140 mg/dL Total bilirubin 2.8 < 1.2 mg/dL Sodium 118 136-145 mmol/L Chloride 86 98-107 mmol/L Bicorbonate 16.8 23-29 mmol/L Creatinine 1.4 0.6-1.3 mg/dL Hemoglobin A1c 11.4 ≤6.5%