Pancreatitis in Patients with Cancer Receiving Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis

Immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (AEs), which pose challenges to the continuation of treatment. Although ICIs are widely used in patients with cancer, studies reporting immune-mediated pancreatitis remain scarce.

We performed a systematic review and meta-analysis to address current knowledge gaps and provide clinical guidance for ICI-associated pancreatitis and lipase elevation.

We searched PubMed/Medline, Embase, and Web of Science for phase 3 randomized controlled trials (RCTs) evaluating ICIs. The incidence of any-grade and grade 3-5 pancreatitis/lipase elevation was calculated. Then, we performed a random-effect model meta-analysis to pool the odds ratios (ORs) of these outcomes using RCTs evaluating the addition of an ICI to systemic therapy to assess the effect of ICIs on pancreatic AEs. A systematic review of the treatment of ICI-related pancreatitis was also conducted.

The incidence analysis included 81 articles (79 RCTs) comprising 36,871 patients. The incidence of treatment-related pancreatitis was 0.68% (any-grade) and 0.32% (grade 3-5). Meta-analysis revealed that the addition of ICI therapy significantly increased any-grade (OR 2.12, 95% confidence interval [CI] 1.45-3.11, p < 0.001) and grade 3-5 pancreatitis (OR 1.76, 95% CI 1.01-3.08, p < 0.05) with low heterogeneity among ICI subtype subgroups (any-grade: I² = 0%, p = 0.99; grade 3-5: I² = 0%, p = 0.63). In analysis of treatment outcome among 146 patients from 53 articles, glucocorticoids were used in 80.6% (n = 108/134) and ICIs were discontinued in 76.5% (n = 101/132; permanent discontinuation: 62.5% [n = 35/56]).

The overall rate of pancreatitis appears low, but the addition of ICI therapy significantly increased the incidence of pancreatitis. These findings provide insight into the incidence and treatment of pancreatitis associated with ICIs.