On October 16, the U.S. Food and Drug Administration (FDA) granted regular approval to venetoclax (Venclexta) in combination with azacitidine, decitabine, or low-dose cytarabine for newly diagnosed acute myeloid leukemia (AML) in adults age 75 or older or who have comorbidities precluding intensive induction chemotherapy. Venetoclax was initially granted accelerated approval for this indication in November 2018.
Efficacy was confirmed in two randomized, double-blind, placebo-controlled trials in patients with AML described above.
VIALE-A and VIALE-C
In VIALE-A, patients were randomly assigned to receive venetoclax plus azacitidine (n = 286) or placebo plus azacitidine (n = 145). Efficacy was established based on an improvement in overall survival. The median overall survival was 14.7 months (95% confidence interval [CI] = 11.9–18.7) in patients treated with venetoclax plus azacitidine compared to 9.6 months (95% CI = 7.4–12.7) in those receiving placebo plus azacitidine (hazard ratio [HR] = 0.66, 95% CI = 0.52–0.85, P < .001). Patients treated with venetoclax plus azacitidine also demonstrated an improvement in complete remission rate: 37% (95% CI = 31%–43%) vs 18% (95% CI = 12%–25%).
In VIALE-C, patients were randomly assigned to receive venetoclax plus low-dose cytarabine (n = 143) or placebo plus low-dose cytarabine (n = 68). Efficacy was based on complete remission rate and duration of complete remission. The complete remission rate in the venetoclax plus low-dose cytarabine arm was 27% (95% CI = 20%–35%) with a median duration of 11.1 months (95% CI = 6.1–not reached) compared to 7.4% (95% CI = 2.4%–16%) with a median duration of 8.3 months (95% CI = 3.1–not reached) in those receiving placebo plus low-dose cytarabine. Venetoclax plus low-dose cytarabine did not significantly improve overall survival vs placebo plus low-dose cytarabine (HR = 0.75, 95% CI = 0.52–1.07, P = .114).
The most common adverse reactions seen in patients treated with venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine (≥ 30% in any trial) were nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, fatigue, vomiting, edema, pyrexia, pneumonia, dyspnea, hemorrhage, anemia, rash, abdominal pain, sepsis, musculoskeletal pain, dizziness, cough, oropharyngeal pain, and hypotension.
The recommended venetoclax dose depends upon the combination regimen and is described in the prescribing information.