On November 21, 2018, the FDA accelerated the approval of venetoclax (Venclexta; AbbVie/Genentech), in combination with azacitidine (Vidaza), decitabine, or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in patients aged ≥75 years or those with comorbidities that preclude intensive induction chemotherapy.
The approval was based on 2 open-label, nonrandomized studies in patients with newly diagnosed AML aged >75 years or those who have comorbidities that preclude intensive induction chemotherapy. The efficacy was based on complete remission (CR) rates and duration.
In the first study of patients receiving venetoclax plus azacitidine, 25 (37%) patients achieved a CR (95% confidence interval [CI], 26-50), with a median remission of 5.5 months. In those receiving venetoclax plus decitabine, 7 (54%) patients achieved a CR (95% CI, 25-81), with a median remission of 4.7 months. In the second study, among 61 patients receiving venetoclax plus low-dose cytarabine, 13 (21%) patients achieved a CR (95% CI, 12-34), with a median remission of 6 months.
The most common (≥30%) side effects with venetoclax plus azacitidine, decitabine, or low-dose cytarabine 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.
Ongoing phase 3 studies are evaluating venetoclax in combination with azacitidine or low-dose cytarabine, with overall survival as the primary end point.