Effect of pembrolizumab on viral hepatitis load and transaminases in advanced hepatocellular carcinoma

INTRODUCTION AND OBJECTIVES: Prospective data are limited regarding viral hepatitis viral load and serology and immunotherapy in patients with hepatocellular carcinoma (HCC). This analysis evaluated hepatitis viral load and serology and transaminase levels in patients with sorafenib-treated advanced HCC who were receiving immunotherapy with pembrolizumab in the KEYNOTE-224 and KEYNOTE-240 studies. MATERIALS AND METHODS: This was a post hoc analysis of the single-arm phase II KEYNOTE-224 (NCT02702414) and the placebo-controlled phase III KEYNOTE-240 (NCT02702401) studies. Patients positive for hepatitis B surface antigen (HBsAg) and/or with detectable hepatitis B virus (HBV), patients positive for isolated total hepatitis B core antibody (anti-HBc), and patients currently or previously infected with hepatitis C virus (HCV) were included. Viral-induced hepatitis flare was defined as >1 log increase from baseline and >1000 IU/ml viral load with concurrent alanine aminotransferase (ALT) elevation classified according to prespecified thresholds. RESULTS: No patient in the pembrolizumab arm who was positive for HBsAg and/or with detectable HBV or who was positive for isolated anti-HBc met the criteria for viral-induced hepatitis flare; 1 patient (3.4%) in the placebo arm met the criteria for viral-induced hepatitis flare. One patient (2.3%) in the pembrolizumab arm of KEYNOTE-240 who was infected with HCV met the criteria for viral-induced hepatitis flare, but the event was not attributed to pembrolizumab. CONCLUSIONS: These results suggest that pembrolizumab does not cause viral-induced hepatitis flare in patients with advanced HCC. GOV IDENTIFIER: NCT02702414 and NCT02702401.