Venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC) has been approved for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) who are age 75 years or older, or who are ineligible for intensive induction chemotherapy.
The decision was based on updated results from the phase III VIALE-A and VIALE-C trials. In the VIALE-A trial, overall survival (OS) for patients who were receiving venetoclax plus azacitidine was 14.7 months, compared with 9.6 months for those receiving placebo plus azacitidine. In addition, the median complete response (CR) duration for patients receiving venetoclax plus azacitidine was 18 months, compared with 13.4 months in the placebo group. Serious adverse events (AEs) included febrile neutropenia (30%), pneumonia (22%), sepsis (excluding fungal; 19%), and hemorrhage (6%).
The VIALE-C trial did not meet its primary endpoint of statistically significant OS improvement for patients with AML who were ineligible for intensive chemotherapy. However, this study was smaller than VIALE-A (it enrolled 211 patients, compared with 431 patients for VIALE-A), and efficacy was supported by an improvement in the rate of CR for patients receiving venetoclax plus LDAC compared with placebo plus LDAC. The median CR rate in the venetoclax arm was 27%, with a median duration of 11.1 months, compared with 7.4% and a median duration of 8.3 months in the placebo group. Serious AEs included pneumonia (17%), febrile neutropenia (16%), and sepsis (excluding fungal; 12%).
Previously, in 2018, the FDA granted accelerated approval to venetoclax combination therapy for this indication.