RESUMEN
BACKGROUND: Pembrolizumab immunotherapy has been associated with hepatotoxicity in 1%-10% of oncology patients treated in clinical trials. AIM: To describe the incidence, phenotypes and outcomes of liver injury in a large cohort of solid organ tumour patients receiving pembrolizumab METHODS: Liver injury was defined by serum alanine aminotransferase, alkaline phosphatase, and/or total bilirubin levels exceeding threshold values. The likelihood of drug-induced liver injury was adjudicated by expert opinion. RESULTS: Seventy (14.3%) of the 491 pembrolizumab-treated patients developed liver injury at a median of 62 days (6-478) and 71.4% had a cholestatic injury profile at onset. The median age, gender and tumour types of liver injury patients were similar to those without, but hepatic metastases (53% vs 21%, P < 0.01) and prior systemic and liver-directed therapy (71% vs 53%, P < 0.01) were more commonly observed in liver injury patients. During follow-up, liver injury patients were less likely to experience tumour remission (10% vs 40.4%) and had higher mortality (67.1% vs 33.7%). Only 20 (28.6%) liver injury cases were adjudicated as probable drug-induced hepatotoxicity; these patients were significantly more likely to present with an hepatocellular/mixed injury pattern (65% vs 12%), to receive corticosteroids (55% vs 12%) and had lower mortality (45% vs 76%) during follow-up. CONCLUSIONS: Oncology patients treated with pembrolizumab who develop liver injury experience poorer outcomes during follow-up. The low incidence of confirmed drug hepatotoxicity highlights the need for thorough medical evaluation before initiating corticosteroids to optimise patient care.
