S5387 Ribociclib-Induced Liver Injury: A Rare Complication of HR-Positive, HER2-Negative Metastatic Breast Cancer Treatment

Introduction: Drug-induced liver injury (DILI) is a leading cause of dose reductions or cycle delays in patients receiving cancer treatment, affecting outcomes and subsequent treatment choices. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are first-line treatment for hormone receptor (HR)-positive, HER2-negative metastatic breast cancers. Ribociclib, a CDK4/6 inhibitor, is an uncommon culprit of DILI. We report a novel case of grade 1 DILI due to ribociclib resulting in grade 4 aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevation. Case Description/Methods: A 54-year-old woman with HR-positive, HER2-negative metastatic breast cancer to bone on ribociclib and anastrozole for 2 months was admitted after outpatient laboratory testing revealed acute hepatitis with aspartate aminotransferase (AST) of 586 U/L and alanine aminotransferase (ALT) of 1,279 U/L. Total bilirubin, alkaline phosphatase, and international normalized ratio (INR) were within normal limits. On review of symptoms, she reported recent fatigue and vomiting. Ribociclib was held the month prior due to grade 1 AST and ALT elevation. She denied alcohol, acetaminophen, or supplement use. Infectious, ischemic, autoimmune, infiltrative, and genetic workup was unrevealing. The etiology was thought to be DILI due to ribociclib, which was discontinued. Her anastrozole was held due to concern for possible contribution. She was re-admitted one week later with worsening AST and ALT to 1,058 U/L and 2,379 U/L, respectively, and hyperbilirubinemia to 1.9 mg/dL. Her INR remained within normal limits. She underwent a liver biopsy which revealed periportal and lobular inflammation, hepatocyte necrosis, and centrilobular necrosis consistent with DILI secondary to ribociclib. There was no plasma cell infiltration concerning for DILI from anastrozole. She was treated with a high-dose prednisone taper for 2 months with normalization of her liver function. Discussion: Our case report demonstrates grade 1 DILI with grade 4 AST and ALT elevation due to ribociclib, an uncommon culprit of DILI. Identifying the culprit drug in a patient receiving multiple anti-cancer agents is difficult. In this case, liver biopsy was critical in elucidating the culprit drug and should be considered in cases where the culprit drug is not clear. Management of CDK4/6 DILI is poorly described, with only 40% of cases treated with steroids. Our case report demonstrates normalization of liver function with a course of steroids, supporting the use of steroids in patients with CDK4/6 inhibitor DILI.