Abstract B066: Asymptomatic Lipase Elevation after Immune Checkpoint Inhibitors Reflects Pancreatic Injury with Volume Loss but Minimal Clinical Sequelae

Abstract Background Immune checkpoint inhibitor (ICI) therapy can cause marked lipase elevation which is frequently asymptomatic (ALE). Guidelines treat ALE as a benign laboratory abnormality without need to hold ICI therapy. We hypothesized that ALE represents pancreatitis evidenced by positive positron emission tomography (PET) scan, and/or volume loss on pancreas volumetry (PV). We assessed clinical outcomes in ALE patients who continued ICI therapy. Methods We conducted a retrospective study of 1,146 ICI-treated patients at MD Anderson with PET/CT within one month of lipase measurement. Asymptomatic patients (n=1,123) were stratified by lipase: normal (n=837), 1–3× upper limit of normal (ULN) (n=222), 3–5× ULN (n=35), and >5× ULN (n=29). Symptomatic patients (n=23) were analyzed separately for comparison. For volumetric analysis (n=117), we included: 1. all PET+/CT+ asymptomatic patients (n=5) and age-, sex-matched asymptomatic patients with normal lipase (n=32) or 1–3× ULN (n=26); 2. all asymptomatic patients with lipase >3× ULN who had follow-up CTs, including PET+/CT+ (n=35); and 3. all symptomatic patients with follow-up CTs, including PET+/CT+ (n=19). Patients who continued ICI therapy were followed for clinical outcomes, including new-onset diabetes, exocrine pancreatic insufficiency (EPI), recurrent lipase elevation or subnormal lipase, pancreatic injury on PET/CT, and symptoms on follow-up. Pancreatic injury was defined as positive PET/CT and/or >20% volume loss. Results In ALE, at baseline, PET detected pancreatic injury more frequently than CT (21.5% vs 10.8%, p=0.016). On volumetry, patients with normal lipase showed no volume loss (73.48 to 67.47 cm3, p=0.386). In the combined <3× ULN group (normal + 1–3× ULN, n=63), PET and CT positivity were uncommon (PET+ 7.9%, CT+ 3.2%), and median pancreatic volume change was minimal (67.87 to 64.24 cm3, p=0.066). In ALE >3× ULN, median pancreatic volume decreased significantly (77.8 to 53.1 cm3, p=7.8×10−6); 57% showed >20% volume loss. Fisher’s exact test confirmed significant differences in >20% volume loss between >3× ULN and <3× ULN ALE (57% vs 21%), p=0.0007). Among symptomatic patients with follow-up CTs (n=19), 67% developed >20% volume loss with median volume decreasing from 73.9 to 49.1 cm3 (p=0.012). Of the 33 patients with ALE who continued ICI therapy, 22 (67%) demonstrated pancreatic injury, yet none developed pancreatitis symptoms. Clinical sequelae, including new-onset diabetes or EPI, were rare. Conclusions ALE following ICI therapy represents a mild form of pancreatitis. Sensitivity to detect pancreatic injury increases progressively from CT to PET to pancreas volumetry. Pancreatic volume loss is seen almost always in those with lipase elevation, frequently >3x ULN. Despite evidence of pancreatic injury, adverse clinical outcomes of continued ICI therapy are rare, supporting the safety of continued ICI therapy. Frequent lipase monitoring may be unnecessary, and evaluation for diabetes and EPI can be performed annually and as clinically indicated, respectively. Citation Format: Hamza A. Chaudhry, Yinghong Wang, Suresh T. Chari. Asymptomatic Lipase Elevation after Immune Checkpoint Inhibitors Reflects Pancreatic Injury with Volume Loss but Minimal Clinical Sequelae [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr B066.