Lenalidomide-Associated Liver Injury With Features of Vanishing Bile Duct Syndrome in Multiple Myeloma.

We report a rare case of lenalidomide-associated hepatotoxicity with histological features suggestive of vanishing bile duct syndrome (VBDS) picture in a woman with multiple myeloma (MM). A 67-year-old woman presented with a three-day history of productive cough, sore throat, fatigue, and pruritus. She has high-risk MM with vertebral metastasis and cord compression, previously treated with palliative radiation. She had received two cycles of treatment with lenalidomide, bortezomib, dexamethasone, and daratumumab, initiated five weeks prior to presentation. She had no history of alcohol use or viral hepatitis. The exam showed scleral icterus and fine left basilar crackles. Labs revealed pancytopenia, hyperbilirubinemia, and elevated liver enzymes. Testing for viral hepatitis and autoimmune markers was negative. Low levels of gamma globulins on serum protein electrophoresis ruled out infiltrative myeloma. Ultrasound and magnetic resonance imaging of the liver were unremarkable. A liver biopsy showed portal fibrosis with obliteration and herniation of portal vein branches, focal mild periductal fibrosis, and mild inflammation of the portal tracts, with some small portal tracts demonstrating missing or atrophic bile ducts. The patient was treated with dexamethasone 4 mg twice daily and ursodeoxycholic acid 600 mg twice daily with serial monitoring of liver function tests (LFTs). Left lower lobe pneumonia was confirmed on chest X-ray and was treated with antibiotics. One week prior, her LFTs were normal. Although aminotransferases downtrended with treatment, bilirubin rose, reaching 13.8 mg/dL. She was discharged on dexamethasone 4 mg daily and ursodeoxycholic acid 600 mg twice daily. Complete bilirubin normalization occurred three months after the discontinuation of lenalidomide when she was restarted on treatment for MM with bortezomib. She is currently being followed up at Saint Peter's Cancer Center with persistent elevation of alkaline phosphatase (ALP). The patient experienced grade 3 hepatobiliary toxicity as per the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. This case highlights VBDS as a manifestation of lenalidomide-induced liver injury with persistent elevation of ALP and histologic findings of bile duct loss in small portal tracts, possibly representing a partial or early form of the condition. Early recognition of this potential hepatotoxicity pattern may guide timely drug discontinuation and appropriate management.