Recurrent Hyperbilirubinemia with Midostaurin during Consolidation in a Patient of AML with FLT3 Mutation and Review of Literature for Alternative Maintenance Strategy

Midostaurin-induced hyperbilirubinemia during consolidation chemotherapy is uncommon. Dose-modification strategy for midostaurin in presence of hyperbilirubinemia remains undefined. We report a case of a young woman diagnosed as acute myeloid leukemia having normal cytogenetics with FLT3-ITD (internal tandem duplication) mutation who tolerated midostaurin during induction but developed recurrent hyperbilirubinemia without transaminitis with midostaurin during high-dose cytarabine consolidation. The pattern of hyperbilirubinemia with midostaurin was transient and rapidly reversible on stopping the drug, but recurred thrice. Sanger sequencing for UGT1A1*28 polymorphism failed to detect relevant variations. In the absence of any other approved FLT3 inhibitor in first line setting, she received sorafenib maintenance at 200 mg twice daily in combination with subcutaneous azacitidine. The combination was well tolerated without hyperbilirubinemia with sorafenib. Safety of sorafenib in the setting of recurrent hyperbilirubinemia with midostaurin is not known. In this case report the combination of sorafenib with parenteral azacitidine was well tolerated without recurrence of hyperbilirubinemia.