Longer Follow-Up Shows Sustained Survival Benefit with Venetoclax and Azacitidine for AML

By Kerri Fitzgerald - December 9, 2022

Two-year follow-up data from the VIALE-A trial showed a sustained benefit in overall survival (OS) in patients with acute myeloid leukemia (AML) who were treated with the combination of venetoclax and azacitidine. The results were presented at the 2022 American Society of Hematology (ASH) Annual Meeting.

The treatment combination is approved by the U.S. Food and Drug Administration to treat patients with intensive chemotherapy-ineligible newly diagnosed AML. The approval was based on earlier phase III results from the VIALE-A study that showed an OS rate of 14.7 months with the venetoclax plus azacitidine combination compared with 9.6 months in patients receiving placebo plus azacitidine (hazard ratio [HR], 0.66; 95% CI, 0.52-0.85; P<.001).

“While the study met the statistical significance for its primary endpoint of OS at the 75% OS interim analysis in March 2020, with 270 OS events, a 100% final OS analysis was undertaken with 360 survival events (data cutoff, December 1, 2021), with two years of additional follow-up to determine the long-term survival benefit of venetoclax plus azacitidine,” the authors noted.

In the longer-term follow-up data presented at ASH, 431 patients with confirmed AML who were treatment-naïve and ineligible for intensive chemotherapy were randomized 2:1 to receive azacitidine 75 mg/m2 subcutaneously or intravenously on days one through seven of 28-day cycles plus venetoclax 400 mg once daily after a three-day ramp up to reach the target dose in cycle one (n=286) or placebo plus azacitidine (n=145).

Median patient age was 76 years in both cohorts; approximately 60% were male, and 76% were white. In the venetoclax plus azacitidine cohort, common mutations included FLT3 (14.1%), IDH1/2 (24.9%), TP53 (23.3%), and NPM1 (16.6%).

After a median follow-up of 43.2 months, median OS was 14.7 months (95% CI, 12.1-18.7) in the venetoclax plus azacitidine cohort versus 9.6 months (95% CI, 7.4-12.7) in the placebo plus azacitidine group (HR, 0.58; 95% CI, 0.47-0.72; P<.001), thus “maintaining the survival benefit since the interim analysis in the overall population,” the authors noted.

At data cutoff, 49 patients remained on study, 48 of whom were in the venetoclax plus azacitidine group.

Among patients who had measurable residual disease (MRD) <10-3 who achieved a complete remission (CR) or CR with incomplete hematologic recovery (CRi), median OS was 34.2 months (95% CI, 27.7-44.0) in the venetoclax plus azacitidine group (n=69) versus 25 months (95% CI, 7.0-39.8) in the placebo plus azacitidine group (n=11). Among patients with an MRD >10-3 who achieved CR/CRi, median OS was 18.7 months (95% CI, 12.9-23.5; n=96) versus 15.1 months (95% CI, 7.4-26.1; n=24), respectively.

For patients with IDH1/2 mutations, median OS was 19.9 months (95% CI, 12.2-27.7) in the venetoclax plus azacitidine group and 6.2 months (95% CI, 2.3-12.7) in the placebo plus azacitidine group (HR, 0.314; 95% CI, 0.189-0.522; P<.001).

Overall safety profiles were comparable between the treatment cohorts. Key any-grade treatment-emergent adverse events (≥20% of patients) included nausea (44.5% vs 36.8%), diarrhea (45.2% vs 34%), and constipation (43.8% vs 39.6%). Grade ≥3 adverse events occurring in ≥10% of patients included thrombocytopenia (45.9% vs 39.6%), neutropenia (42.8% vs 28.5%), and febrile neutropenia (42.8% vs 18.8%). Serious adverse events occurred in 85.1% of patients in the venetoclax plus azacitidine group and 77.1% in the placebo plus azacitidine cohort.

“The VIALE-A two-year follow-up analysis confirms the long-term survival benefit for patients treated with venetoclax plus azacitidine, with no new safety findings,” the authors concluded. Further characterization of patients with long-term benefit is ongoing.


Pratz KW, Jonas BA, Pullarkat VA, et al. Long-term follow-up of the phase 3 Viala-A clinical trial of venetoclax plus azacitidine for patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Abstract #219. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.

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