Evaluation of liver enzyme elevations and hepatotoxicity in patients treated with checkpoint inhibitor immunotherapy.

Abstract

Background and aimsImmune checkpoint inhibitors (ICI) are increasingly used in cancer therapy. Elevated liver enzymes frequently occur in patients treated with ICI but evaluation is poorly described. We sought to better understand causes of liver enzyme elevation, investigation and management.MethodsPatients treated with anti-PD-1, PDL-1 or CTLA-4 therapy in Phase I/II clinical trials between August 2012 and December 2018 were included. Clinical records of patients with significant liver enzyme elevations were retrospectively reviewed.ResultsOf 470 ICI-treated patients, liver enzyme elevation occurred in 102 (21.6%), attributed to disease progression (56; 54.9%), other drugs/toxins (7; 6.9%), other causes (22; 21.6%) and ICI immunotoxicity (17; 16.7%; 3.6% of total cohort). Immunotoxicity was associated with higher peak ALT than other causes of enzyme elevation (N = 17; M = 217, 95% CI 145-324 for immunotoxicity, N = 103; M = 74, 95% CI 59-92 for other causes; ratio of means 0.34, 95% CI 0.19-0.60, p = ConclusionsLiver enzyme elevation is common in patients receiving ICI, but often has a cause other than immunotoxicity. A biochemical signature with higher ALT and ALT/AST ratio, a history of prior ICI exposure and other organ immunotoxicities may help to identify patients at a higher likelihood of immunotoxicity. Liver biopsy can be safely deferred in most patients. We propose an approach to diagnostic evaluation in patients with liver enzyme elevations following ICI exposure.