Immune Checkpoint Inhibitor-related Pancreatitis: A Case Series, Review of the Literature and an Expert Opinion

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies, but are associated with serious adverse events like pancreatitis. Current guidelines are limited to the first step in treating acute ICI-related pancreatitis with steroids but lack treatment advices for steroid dependent pancreatitis. We describe a case series of 3 patients who developed ICI-related pancreatitis with chronic features such as exocrine insufficiency and pancreatic atrophy at imaging. Our first case developed after treatment with pembrolizumab. The pancreatitis responded well after discontinuation of immunotherapy but imaging showed pancreatic atrophy and exocrine pancreatic insufficiency persisted. Cases 2 and 3 developed after treatment with nivolumab. In both, pancreatitis responded well to steroids. However during steroid tapering, pancreatitis recurred and the latter developed exocrine pancreatic insufficiency and pancreatic atrophy at imaging. Our cases demonstrate resemblances with autoimmune pancreatitis based on clinical and imaging findings. In line, both diseases are T-cell mediated and for autoimmune pancreatitis azathioprine is considered as maintenance therapy. Guidelines of other T-cell mediated diseases like ICI-related hepatitis suggest tacrolimus. After adding tacrolimus in case 2 and azathioprine in case 3, steroids could be completely tapered and no new episodes of pancreatitis have occurred. These findings support the idea that the treatment modalities for other T-cell mediated diseases are worthwhile options for steroid dependent ICI-related pancreatitis.

Asymptomatic pancreatic enlargement without pancreatic enzyme elevation: a rare case of immune checkpoint inhibitor-associated pancreatitis

“…Guidelines for other immune-related adverse events [ 12 ], such as ICI-related hepatitis, suggest adding mycophenolate mofetil and/or tacrolimus for steroid refractory cases. Kramer et al [ 13 ] used those drugs as maintenance therapy for steroid refractory ICI-associated pancreatitis with favorable outcomes. Clinicians should consider the fact that patients receiving ICI therapy have advanced malignancies, and future studies should evaluate the optimal treatment timing and strategy.…”

Review article: Contemporary management of gastrointestinal, pancreatic and hepatic toxicities of immune checkpoint inhibitors

“…Limited evidence suggests that infliximab may be used in patients with steroid-refractory ICI pancreatic injury; one case report described the resolution of acute pancreatitis with infliximab after multiple failed steroid tapers. 124 Successful uses of rituximab 125 and azathioprine 126 have also been reported in at least one case report each of steroid-refractory ICI pancreatitis. The potential utility of other steroid-sparing agents for ICI pancreatitis is an open area of investigation, as data remain extremely limited and guidelines do not opine on their use.…”