Asymptomatic Lipase Elevation after Immune Checkpoint Inhibitors Reflects Pancreatic Injury with Volume Loss but Minimal Clinical Sequelae

OBJECTIVES: Asymptomatic lipase elevation (ALE) following immune checkpoint inhibitor therapy (ICI-℞) is considered a laboratory abnormality distinct from clinical pancreatitis. We hypothesized that ALE indicates pancreatic injury defined as imaging evidence of pancreatitis on CT/PET scans and/or volume loss on CT pancreatic volumetry (PV). We examined the safety of continued ICI-℞ in ALE. METHODS: We identified 1,146 ICI-treated patients with PET/CT and lipase measurement within one month. Asymptomatic patients (n=1,123) were stratified by lipase levels: normal (n=837), 1-3× (n=222) or ≥3× (n=64) upper limit of normal (ULN). We compared pancreas volume (baseline vs. 1-year and % with ≥20% volume loss) in 98 patients across these strata. Clinical sequelae (pancreatitis, endocrine/exocrine insufficiency) were recorded for patients continuing ICI-℞. RESULTS: Normal lipase cohort showed no evidence of pancreatic injury. In ALE with lipase 1-3×ULN, CT/PET rarely showed pancreatitis (0.5%/2%); ≥20% volume loss occurred in 28%. In ALE with lipase ≥3×ULN, CT+/PET+/≥20% volume loss were seen in 9%/16%/57%, respectively (P<0.0001 for each feature vs 1-3x ULN). Pancreas volume (median) decreased significantly in lipase ≥3× (P<.0001). Continuing ICI-℞ in patients with ALE (n=33) and symptomatic pancreatitis (n=5) resulted in minimal to no clinical sequelae. CONCLUSIONS: ALE following ICI-℞ indicates pancreatic injury characterized best by volume loss. Despite this, therapy continuation is well tolerated with minimal clinical sequelae. While our data doesn't change current management, they do suggest that ALE and ICI-P represent a clinical spectrum of a shared pathophysiology.