DiNardo Discusses VIALE-A and Venetoclax Combo in AML

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Today, we had the pleasure of speaking with Courtney DiNardo, MD, MSCE, clinical researcher in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, to discuss the results of the phase 3 VIALE-A trial in acute myeloid leukemia (AML).

In November 2018, the FDA granted an accelerated approval to venetoclax (Venclexta) for use in combination with azacitidine, decitabine, or low-dose cytarabine for the treatment of adult patients with newly-diagnosed AML who are aged 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy, based on the results from 2 phase 1b/2 trials in this setting.

During the 2020 European Hematology Association Congress, DiNardo presented the results of the VIALE-A trial, in which the combination of venetoclax and azacitidine led to a 34% reduction in the risk of death versus azacitidine alone in treatment-naïve patients with AML who are ineligible for intensive therapy.

At a median follow-up of 20.5 months, the median overall survival (OS) was 14.7 months with venetoclax and azacitidine versus 9.6 months with azacitidine and placebo, translating to a 44% reduction in the risk of death.

VIALE-A is the first phase 3 study in older unfit patients with newly diagnosed AML to show a survival benefit of this magnitude, DiNardo said, adding that the combination should be considered a new standard of care for older patients who are not eligible for standard intensive chemotherapy.

Additionally, the complete response rate with venetoclax and azacitidine was more than double that of azacitidine/placebo, at 36.7% and 17.9%, respectively.

Moreover, responses favored the addition of venetoclax, irrespective of cytogenetic risk or molecular subgroup.

The observed toxicities weree consistent with the known safety profile of the combination of venetoclax and azacitidine and those of each agent alone. The most common all-grade gastrointestinal adverse effects (AEs) in the venetoclax/azacitidine and azacytidine/placebo arms, respectively, included nausea, constipation, diarrhea, and vomiting.

Serious AEs in the venetoclax/azacitidine and azacitidine/placebo arms consisted of febrile neutropenia and pneumonia.

Grade 3 or higher hematological AEs consisted of thrombocytopenia, neutropenia, febrile neutropenia, anemia, and leukopenia.

DiNardo added that with the combination, bone marrow biopsies should be performed at the end of cycle 1 as opposed to 3 or 4 months into treatment with azacitidine alone.

In our exclusive interview, Dr. DiNardo discussed the role of venetoclax in AML and explained the significance of the results of the VIALE-A trial.