The Lynx Group

Venetoclax plus Azacitidine Combination Improves Overall Survival in Patients with AML

October 2020, Vol 11, No 5

The prognosis of older patients with acute myeloid leukemia (AML) has been poor, even after treatment with a hypomethylating agent. A previous phase 1b study of azacitidine (Vidaza) added to venetoclax (Venclexta) showed promising efficacy and duration of response in treatment-naïve patients with AML who were ineligible for chemotherapy.

In a new study, researchers report findings from a confirmatory clinical trial that evaluated the efficacy and safety of this combination regimen in treatment-naïve patients with AML who were ineligible for intensive induction therapy (DiNardo CD, et al. N Engl J Med. 2020;383:617-629).

The VIALE-A study was a multicenter, randomized, double-blind, placebo-controlled, phase 3 clinical trial of 433 patients with confirmed AML who were ineligible for intensive therapy because of comorbidities, aged ≥75 years, or both. The exclusion criteria included patients who had received previous treatment with a hypomethylating agent for an antecedent hematologic disorder.

Patients were randomized in a 2:1 ratio to azacitidine plus venetoclax (N = 286) or to azacitidine plus placebo (N = 145). All patients received a standard dose of azacitidine (75 mg2/kg subcutaneously on days 1 through 7 every 28-day cycle); venetoclax (target dose, 400 mg) or matching placebo was administered orally, once daily in 28-day cycles. The primary end point was overall survival (OS). The secondary end points included composite complete remission.

With a median follow-up of 20.5 months, the median OS was 14.7 months in the azacitidine plus venetoclax arm versus 9.6 months in the azacitidine plus placebo arm (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P <.001).

Overall, 66.4% of the patients in the active combination arm achieved composite complete remission (complete remission or complete remission with incomplete hematologic recovery) compared with only 28.3% in the placebo arm. The treatment responses were also rapid and durable, with 43% of patients in the azacitidine plus venetoclax arm showing a response during the first cycle of treatment, and a median duration of remission of 17.5 months.

The combination of azacitidine plus venetoclax has a safety profile similar to that of each drug alone. The most common adverse events in both groups included hematologic and gastrointestinal events, and rates of adverse events were generally consistent between both treatment arms. However, higher rates of grade ≥3 neutropenia (42% vs 28%) and febrile neutropenia (42% vs 19%) were observed in the active combination arm compared with the azacitidine and placebo arm.

“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,” the researchers noted, emphasizing the importance of monitoring and managing myelosuppression in patients who are receiving this combination therapy.

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