Among older patients with acute myeloid leukemia (AML) who have not received any previous therapy and were ineligible for standard induction chemotherapy, those treated with azacitidine and venetoclax had superior overall survival and incidence of remission compared with patients who were treated with azacitidine alone, according to study results published in The New England Journal of Medicine.

 A team of investigators conduced a phase 3, multicenter, randomized double-blind, placebo-controlled trial (VIALE-A; Identifier: NCT02993523) to determine the efficacy and safety of combination azacitidine and venetoclax therapy compared with azacitidine and placebo in patients with AML who were not eligible to receive intensive induction chemotherapy due to coexisting conditions, age, or both.

Participants included in the study were randomly assigned to receive either azacitidine-venetoclax treatment or azacitidine-placebo. Patients in both arms received standard doses of azacitidine (75 mg per square meter of body surface area). Azacitidine was administered either subcutaneously or intravenously. Participants were also administered either oral venetoclax treatment (400 mg target dose) or the placebo equivalent once a day. The main outcome of the study was overall survival.

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A total of 431 participants were included in the study (286 in the azacitidine-venetoclax group and 145 in the azacitidine-placebo group). Both groups had a median age of 76 years (range, 49-91 years). The median follow-up was 20.5 months.

The median overall survival in the azacitidine-venetoclax and azacitidine-placebo groups were 14.7 months and 9.6 months, respectively (hazard ratio for death, 0.66; 95% CI, 0.52-0.85; P <.001).

The incidence of complete remission and composite complete remission were both higher in the azacitidine-venetoclax group (P <.001 for both) compared with the placebo group.

Nausea of any grade was reported in 44% of patients in the azacitidine-venetoclax arm and in 35% of patients in the placebo arm. Among azacitidine-venetoclax and placebo groups, other adverse events included grade 3 or greater thrombocytopenia (45% and 38%, respectively), neutropenia (42% and 29%, respectively), and febrile neutropenia (42% and 19%, respectively). In addition, 85% of azacitidine-venetoclax group members and 67% of control group members had infections of any grade.

“The safety profile of azacitidine plus venetoclax was consistent with the known side effect profiles of both agents, and adverse events were consistent with expectations for an older AML population,” the authors noted.

“The combination of azacitidine plus venetoclax in this challenging patient population in this trial was an effective treatment regimen that led to significant improvements in the incidence of composite complete remission and overall survival. Unlike monitoring of patients who receive azacitidine alone, ongoing attentiveness to the monitoring and management of myelosuppression is key for patient safety with this combination therapy,” the investigators concluded.

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


DiNardo CD, Jonas BA, Pullarkat MJ, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383:617-629. doi:10.1056/NEJMoa2012971

This article originally appeared on Hematology Advisor