Fatal Immune Checkpoint Inhibitor-related Pancreatitis

Abstract

We herein report a case of fatal pancreatitis induced by an immune checkpoint inhibitor. A 62-year-old man with cancer of unknown primary was treated with pembrolizumab. After 12 cycles, immune-related pneumonitis developed and was treated with prednisolone. Three months later, pancreatitis developed, which was successfully treated with hydration and protease inhibitors. Eight months later, another attack of pancreatitis occurred, which did not respond to therapy, including high-dose corticosteroids, and he eventually died. This is the first report describing fatal immune checkpoint inhibitor-related pancreatitis. Despite the rarity of this complication, attention should be paid to its potential severity and treatment.

Keywords: acute pancreatitis; drug-induced pancreatitis; immune checkpoint inhibitor; immune-related adverse event; pembrolizumab.

Figure 1.

Pretreatment radiological findings. (a) CT reveals swollen lymph nodes (arrowheads) around the aorta. (b) No abnormal findings are seen in the pancreas. The yellow circle represents a swollen lymph node. (c) PET reveals an increased uptake of FDG in the lymph nodes; the maximum standardized uptake value (SUVmax) is 11.7.

Figure 2.

CT findings at the first pancreatitis episode (pancreatic phase of dynamic enhanced CT). Fluid collection is present around the pancreas.

Figure 3.

Clinical course for the first bout of pancreatitis. After admission, the patient was treated with hydration and fentanyl. CRP and WBC decreased, but the pancreatic enzyme values did not normalize. PI: protease inhibitor

Figure 4.

CT findings for the second pancreatitis episode (on day 8, dynamic enhanced CT). (a) Arterial phase. Fluid collection is present around the pancreas. The attenuation of the pancreatic body and tail is relatively low. (b) Delayed phase. The fluid collection extends to the pelvis.

Figure 5.

Clinical course of the second episode of pancreatitis. The patient was discharged and readmitted on day 8. Thereafter, the total bilirubin values continued to increase. On day 20-22, intravenous methylprednisolone (1,000 mg/day for 3 days) was given, followed by oral prednisolone (60 mg/day). The patient died on day 33. PI: protease inhibitor

Figure 6.

MRI findings for the second bout of pancreatitis. A coronal T2-weighted MR image (a) and magnetic resonance cholangiopancreatography (b) demonstrate the narrowing of the intrapancreatic bile duct (arrowhead) and main pancreatic duct (arrow) in the enlarged pancreatic head.

Figure 7.

CT findings after treatment with corticosteroids. Dilatation of the intrahepatic biliary ducts is seen. Stricture of the supra-pancreatic biliary tree is absent.