Venetoclax-Azacitidine Combo Improves OS, Appears Safe for Certain Patients with AML


The multi-institution trial randomized patients with acute myeloid leukemia to receive either a combination of venetoclax and azacitidine or azacitidine plus placebo.

Results from the phase 3 VIALE-A trial demonstrated that a combination regimen of venetoclax (Venclexta) and azacitidine (Vidaza) was safe and improved overall survival (OS) over azacitidine alone in certain patients with acute myeloid leukemia (AML).1

The results were presented at the virtual 25th European Hematology Association (EHA) Annual Congress and were also recently published in the New England Journal of Medicine.

“A large portion of patients with AML, including those older than 75 or those who have medical comorbidities, cannot tolerate existing treatment strategies, and the patients with AML who are ineligible for intensive chemotherapy often experience poor prognoses,” Courtney D. DiNardo, MD, lead investigator and associate professor of Leukemia at The University of Texas MD Anderson Cancer Center, said in a press release.2 “We launched the VIALE-A trial to evaluate whether we could safely use a combination therapy to treat this critical patient population.”

In the multi-institution trial, the intent-to-treat population included 431 patients who were randomized 2:1 to receive either the combination of venetoclax and azacitidine (n = 286) or azacitidine plus placebo (n = 145). The primary end point was OS.

At a median follow-up of 20.5 months, the median OS was 14.7 months in the combination group and 9.6 months in the control group (HR, 0.66; 95% CI, 0.52-0.85; P < .001). Overall, the incidence of complete remission (CR) was higher with the combination than with the control regimen (36.7% vs. 17.9%; P < .001), as was the composite CR, defined as CR or CR with incomplete hematologic recovery (66.4% vs. 28.3%; P < .001).

Notable adverse events (AEs) in the combination and monotherapy groups included nausea of any grade (44% vs 35%, respectively) and grade 3 or higher thrombocytopenia (45% vs 38%), neutropenia (42% vs 28%), and febrile neutropenia (42% vs 19%). Moreover, infections of any grade occurred in 85% of the patients in the azacytidine-venetoclax group and 67% of those in the control group. Serious AEs occurred in 83% and 73%, respectively.

“The primary adverse events seen with azacitidine and venetoclax are related to increased cytopenias, including neutropenia and neutropenia-related infections,” DiNardo explained in the release. “Key management guidelines include dosing interruptions between cycles to allow for count recovery in the setting of a leukemia-free marrow, and the use of granulocyte colony-stimulating factor as an adjunct to improve neutrophil count once a patient is in remission.”

Though there is not currently a reliable standard treatment regimen for patients with AML, the researchers indicated that this study is likely to be practice-changing for the treatment of some groups of patients with AML. However, additional research is necessary to determine how new therapies, including this combination therapy, can improve outcomes for all patients with AML.

“While this combination represents a key advance in AML therapy, improving both remission and survival rates in newly diagnosed patients with AML, many unfortunately will still relapse,” said DiNardo. “Our next steps include an evaluation of azacitidine and venetoclax as a backbone to which additional novel therapeutics are being evaluated in particularly high-risk populations."


1. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. New England Journal of Medicine 2020; 383:617-629. doi: 10.1056/NEJMoa2012971.

2. Combination therapy significantly improves survival outcomes for patients with acute myeloid leukemia [news release]. Houston. Published August 12, 2020. Accessed August 13, 2020.

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