Azacitidine Therapy Plus Venetoclax Shows Promising Activity in AML

For adults with previously untreated acute myeloid leukemia (AML) ineligible for induction therapy, adding venetoclax to azacitidine yielded higher rates of overall survival (OS) and remission (N Engl J Med. 2020;383[7]:617-629).

“Older patients with [AML] have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine added to venetoclax had promising efficacy in a previous phase 1b study,” reported Courtney DiNardo, MD, University of Texas MD Anderson Cancer Center, Houston, and colleagues.

A total of 431 patients (median age, 76) with untreated AML were included in a randomized trial by Dr DiNardo et al, including 285 patients given azacitidine plus venetoclax and 145 given azacitidine plus placebo.

Patients were given the standard dose of azacitidine (75 mg/m2 of body-surface area on days 1 through 7 of every 28-day cycle) with venetoclax 400 mg or matching placebo.

The primary end point of the study was OS.

Findings showed that the median OS of patients given azacitidine plus venetoclax was 14.7 months, while the control group had a median OS of 9.6 months (hazard ratio [HR], 0.66; 95%, CI, 0.52-0.85; P <.001).

The rates of complete remission were 36.7% and 17.9% (P <.001) for recipients of azacitidine plus venetoclax versus azacitidine alone, respectively. The composite complete remission rates were also higher with azacitidine plus venetoclax (66.4%) versus azacitidine-venetoclax (23.8%).

Adverse events occurring in patients given azacitidine plus venetoclax versus azacitidine alone included nausea of any grade (44% vs 35%, respectively), grade ≥3 neutropenia (42% vs 28%), febrile neutropenia (42% vs 28%), and thrombocytopenia (45% vs 38%). Infections of any grade and serious adverse events also occurred in both arms.

“In previously untreated patients who were ineligible for intensive chemotherapy, [OS] was longer, and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone,” concluded Dr DiNardo et al.—Alexandra Graziano