Severe Hepatotoxicity due to Ibrutinib with a Review of Published Cases

Ibrutinib, an irreversible Bruton’s tyrosine kinase inhibitor, is an effective treatment for Waldenström’s macroglobulinemia, chronic lymphocytic leukemia, and several other types of lymphoma. Studies prior to FDA approval in 2015 failed to demonstrate any hepatotoxicity. However, since then, there have been 2 reports in the literature of severe hepatic injury. We present a third case of a 77-year-old woman presenting with nausea and jaundice after recent discontinuation of ibrutinib and compare the presentation as well as course of all 3 known cases. The sudden onset of acute hepatotoxicity is idiosyncratic, occurring weeks after starting ibrutinib treatment. Liver biopsies in all cases revealed mixed hepatocellular and cholestatic features. Improvement progressed slowly upon discontinuation of ibrutinib. Awareness of ibrutinib hepatotoxicity, periodic surveillance of liver function tests, early recognition of any abnormalities, and prompt discontinuation of the medication are recommended.