The U.S. Food and Drug Administration (FDA) granted accelerated approval to the BCL2 inhibitor venetoclax, in combination with azacitidine or decitabine or low-dose cytarabine, for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults aged 75 years or older or who have comorbidities that preclude use of intensive induction chemotherapy.
The approval is based on results from two phase II trials. The M14-358 study evaluated venetoclax in combination with azacitidine (n=67) or decitabine (n=13) in patients with newly diagnosed AML. In combination with azacitidine, 25 patients achieved a complete remission (CR) with a median observed time in remission of 5.5 months (range = 0.4-30 months). In combination with decitabine, seven patients achieved a CR, with a median observed time in remission of 4.7 months (range = 1.0-18 months).
The M14-387 study evaluated venetoclax in combination with low-dose cytarabine in patients with newly-diagnosed AML (n=61), including patients with previous exposure to a hypomethylating agent for an antecedent hematologic disorder. When combined with low-dose cytarabine, treatment with venetoclax induced CR in 13 patients, with a median observed time in remission of six months (range = 0.03-25 months).
The most common adverse reactions (≥30%) associated with venetoclax were nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, fatigue, vomiting, peripheral edema, pneumonia, dyspnea, hemorrhage, anemia, rash, abdominal pain, sepsis, back pain, myalgia, dizziness, cough, oropharyngeal pain, pyrexia, and hypotension.
Source: FDA news release, November 23, 2018.