S123 Pancreatic Injury Underlies Asymptomatic Lipase Elevation Induced by Immune Checkpoint Inhibitors

Introduction: Marked lipase elevations, often asymptomatic, occur due to immune checkpoint inhibitor (ICI) therapy. Asymptomatic lipase elevation (ALE) is managed differently than cases meeting criteria for pancreatitis. In ICI-treated patients we sought evidence of pancreatic injury on computed tomography scan (CT), positron emission tomography scan (PET), and through pancreas volumetry (volume increase at lipase elevation and loss on follow-up). Methods: We assembled a retrospective cohort of 1,146 ICI-treated patients who had a PET/CT within 1 month of peak serum lipase. We correlated PET and CT positivity with lipase levels. In a subset of 52 patients with lipase >3× the upper limit of normal (ULN), we performed serial pancreas volumetry on CT scans obtained before, at, and within 1 year of peak lipase elevation (LE). Results: PET positivity was rarely seen in those with lipase levels <3× ULN (1.02%) vs those with lipase >3× ULN (37.68%). In the volumetry cohort, 41/52 (80%) patients were asymptomatic; 25 (48%) were PET+, and 16 (31%) were CT+. We observed no increase in pancreatic volume at peak LE in any group (P = 0.4). However, substantial pancreatic volume loss developed within a year. Mean volume ± SD before and after peak LE in PET+/CT+ (n = 16), PET+/CT- (n = 9), and asymptomatic PET-/CT- (n = 27) patients was 76.3 ± 13 vs 45.8 ± 18 (P = 0.0014), 58.3 ± 14 vs 41.1 ± 17 (P = 0.0012), and 81.9 ± 7 vs 63.9 ± 10 (P = 0.0002), respectively. Among patients with lipase >3× ULN, >15% volume loss was seen in 72.4%, PET-positivity in 43.1% and CT-positivity in 27.6%. In asymptomatic lipase elevation (n = 41) 73% had >15% volume loss (before vs after: 77.6 ± 6 vs 55.9 ± 8, P = 4.28E-07). Conclusion: Asymptomatic lipase elevation after ICI treatment indicates pancreatic injury, despite not meeting criteria for pancreatitis. In those with >3× ULN lipase elevations, vast majority lose pancreatic volume on follow-up, though only a minority have changes on CT or PET. Mechanism of ICI-induced pancreatic injury needs further study.