1395 Nivolumab-Induced Hemorrhagic Pancreatitis

Abstract

INTRODUCTION: The checkpoint inhibitor nivolumab is an anti-PD-1 monoclonal antibody (mAb) that treats malignancy. Increased usage of checkpoint inhibitors has led to an increasing incidence of immune-related adverse events (irAEs) such as immune checkpoint inhibitor-induced pancreatic injury (ICIPI). We report a case of nivolumab-induced pancreatitis that progressed to fatal hemorrhagic pancreatitis. CASE DESCRIPTION/METHODS: A 61-year-old man diagnosed with small cell lung cancer with brain, adrenal, and osseous metastases presented with a one-day history of epigastric pain radiating to the back after starting a biweekly dose of nivolumab forty days prior. On admission, he had a lipase of 2700 U/L. His abdominal CT scan was consistent with acute interstitial pancreatitis. The patient was treated with hydromorphone as needed and Lactated Ringer's. He was continued on his home dexamethasone and discharged. Fourteen days after initial presentation, the patient reported increased abdominal cramping. MRCP findings were consistent with acute hemorrhagic pancreatitis with organizing complex peripancreatic fluid collections. He became febrile and hypoxic, and twenty-three days after initial presentation, chest CT scans showed acute respiratory distress syndrome or multifocal pneumonia. The patient decompensated and eventually died of cardiopulmonary failure secondary to hemorrhagic pancreatitis and worsening of his underlying malignancy. DISCUSSION: Nivolumab is a PD-1 mAb that works by enhancing the T-cell response to malignancies. Checkpoint inhibitors are known to cause irAEs including ICIPI due to their increased immune activation. However, reports of nivolumab-related pancreatitis are rare, with a reported rate of <1%. While anti-PD-1 mAbs often cause asymptomatic pancreatic enzyme elevations, nivolumab-related pancreatitis may also progress to serious complications, such as pseudocyst or chronic pancreatitis. The mainstay of treatment for irAEs is a combination of immunosuppression with glucocorticoids and/or a removal of the checkpoint inhibitor, depending on the severity of the irAE. Expert opinion currently guides steroid and checkpoint inhibitor management based on the intensity of the reaction: at lower severity the drug can either be stopped temporarily or not at all. This case adds to the growing presentations of nivolumab-induced pancreatitis. Though the incidence of pancreatitis as a result of checkpoint inhibition remains low, the progression to severe disease is possible.