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Malek Ayoub*, Scott R. Anderson, Vanisha Patel, Motaz Ashkar
Gastroenterology Department, Washington University in St Louis, St Louis, MO

Introduction: Immune-related adverse events (irAE) are increasingly noted with the use of immune checkpoint inhibitors (ICI), with enterocolitis and hepatitis being the most common gastrointestinal manifestations. Pancreas-specific irAEs are rarer and occur in 2.22% of patients. It has a vast array of manifestations including asymptomatic elevation of pancreatic enzymes, asymptomatic radiologic pancreatic inflammation, and rarely acute pancreatitis. Based on the revised Atlanta classification, Ashkar et al proposed a novel classification of pancreas-specific irAEs in cancer patients as types I-III pancreatic injury and acute pancreatitis (AP).

Case Description: This case series describes the clinical course of ten cancer patients who were treated with ICI (pembrolizumab, nivolumab, or a combination of both) and subsequently developed pancreas-specific irAEs. Four patients had mild AP, of which three patients developed pancreatic atrophy and required treatment for exocrine pancreatic insufficiency (EPI). Six patients developed pancreatic injury, with two patients demonstrating type II injury and four with chronic pancreatic injury. Of these patients, four were noted to have progressive pancreatic atrophy (Figure 1), and five developed EPI requiring pancreatic enzyme replacement therapy (PERT). Five patients received corticosteroids for non-pancreatic irAEs, and two patients for pancreas-specific irAEs. Baseline hemoglobin A1C levels were not available in all patients, but five developed pre-diabetes after ICI therapy initiation. One patient underwent endoscopic ultrasound-guided pancreatic fine needle biopsies, demonstrating pancreatic acinar and ductal acute inflammation with focal apoptosis.

Discussion: Despite promising anticancer properties, ICI toxicities are common. Given the rarity of pancreas-specific irAEs, these adverse events remain poorly studied. Importantly, few studies have correlated hyperamylasemia or hyperlipasemia with clinical outcomes. Recent work reported 2.7% of asymptomatic hyperlipasemia after ICI, whereas AP was 1.9%. Ashkar et al examined the degree and duration of ICI treatment in causing pancreas-specific irAEs and proposed a novel disease classification, which defined AP based on the revised Atlanta classification criteria. Additionally, pancreatic injury was stratified into three groups if not fitting AP criteria based on biochemical enzymatic elevations, clinical presentation, and radiological inflammatory changes (Table 1). Our case series highlights important clinical features of pancreas-specific irAEs and applied Ashkar et al's classification for categorizing pancreatic injury. Early recognition of pancreas-specific irAEs enables effective management and potentially can mitigate long-term pancreatic dysfunction.

Normal Pancreas (On the left) and Pancreatic Atrophy (On the right) post-immune checkpoint inhibitors (ICI) therapy.

Ashkar et al's novel classification for immune checkpoint inhibitors (ICI) pancreas-specific adverse events.

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