Azacitidine Combined With Low Dose Venetoclax and Azole in Treatment-Naive, Elderly Patient with Acute Myeloid Leukemia: A Case Report

We report the case of a 70-year-old frail patient with AML-M0, normal karyotype and negative FLT3 and NPM1, treated successfully with the combination of Azacitidine (75 mg/m2 D1-D7) and Venetoclax (100 mg D1-D14) in whom Fluconazole was added to potentiate the effect of Venetoclax in vivo, reaching a Complete Remission. Venetoclax is metabolized by the CYP3A. When administered with strong CYP3A inhibitors, such as azoles, drug’s concentration will increase by 2-7 folds empowering its effect. Considering the inadequate accessible dose of Venetoclax and the current Lebanese economic crisis, 200 mg of daily Fluconazole, a moderate CYP3A4 inhibitor, was combined to Venetoclax to increase its bioavailability. The patient reached a complete remission after four cycles. He presented grade I febrile neutropenia after the first two cycles. No major adverse events were reported. We believe it’s the first case reporting a complete remission after combining low dose Venetoclax, Azacitidine and a moderate CYP3A inhibitor.