Characteristics and outcomes of low-grade and high-grade pancreatic immune-related adverse events at a single center

Abstract

Objective

Immune checkpoint inhibitors (ICIs) are widely utilized in treating various malignancies but are associated with immune-related adverse events (irAEs), which often poses challenges to their use. Pancreatic irAEs, though rare, can present as new-onset diabetes, pancreatitis, or asymptomatic lipase elevation, often altering the clinical trajectory and quality of life of patients. This study sought to expand the understanding of this rare toxicity by summarizing the characteristics and outcomes of low-grade and high-grade pancreatic irAEs.

Methods

We conducted a single-center, retrospective study of adult patients treated with checkpoint inhibitors between 2010 and 2022. Patients with clinical or radiographic evidence of pancreatic injury associated with ICI therapy were included. Pancreatic irAEs were defined as low-grade (< grade 3) or high-grade (≥ grade 3) using the Common Terminology Criteria for Adverse Events.

Results

Of 21 patients identified with pancreatic irAEs, 76% (n = 16) experienced high-grade severity, often requiring hospitalization. The majority of patients presented with either new-onset diabetes (n = 11) or pancreatitis (n = 11). Most low-grade irAEs resolved, while the majority of high-grade events did not, particularly due to the lasting nature of insulin-dependent diabetes. ICI rechallenge was attempted in most cases, although conclusions regarding subsequent disease and survival outcomes are limited.

Conclusions

Pancreatic irAEs, though uncommon, often present at higher toxicity grades at onset and require substantial medical intervention, whether acutely in the hospital or longitudinally in the outpatient setting. Early identification and management remain critical, and ICI rechallenge appears to be feasible in select patients. Further research is required to better predict and manage severe pancreatic irAEs.