Severe Lenalidomide-Associated Hyperbilirubinemia

Immunomodulatory drugs (IMids), such as thalidomide and lenalidomide, are used to treat plasma cell neoplasms and B-cell malignancies. We present a case of severe direct hyperbilirubinemia in a patient taking lenalidomide-based therapy for plasmacytoma. Imaging was unrevealing, and liver biopsy showed only mild sinusoidal dilation. Roussel Uclaf Causality Assessment (RUCAM) score was 6, indicating lenalidomide was a probable cause of the injury. To our knowledge, this is the highest reported direct bilirubin regarding lenalidomide drug-induced liver injury (DILI), with a peak bilirubin of 41mg/dL. While a clear pathophysiology was not identified, this case provides important considerations regarding lenalidomide safety.