In the study, a team of researchers conducted a phase III, multicenter, randomized, double-blind, placebo-controlled trial to ascertain the efficacy and safety of combination azacitidine and venetoclax therapy compared with azacitidine and placebo in patients with AML who were not eligible to receive intensive induction chemotherapy due to coexisting conditions, age, or both.
Participants in the study were randomly assigned to receive either the azacitidine-venetoclax treatment or azacitidine-placebo. Patients in both arms received standard doses of azacitidine (75 mg per square meter of body surface area). Azacitidine was administered either SC or IV. Patients were also administered either oral venetoclax treatment (400-mg target dose) or the placebo equivalent once a day.
The major outcome of the study was overall survival. A total of 431 participants were included in the study (286 in the azacitidine-venetoclax group and 145 in the azacitidine-placebo group). Both groups had an average age of 76 years (range 49-91 years). The median follow-up was 20.5 months. The average overall survival in the azacitidine-venetoclax and azacitidine-placebo groups were 14.7 months and 9.6 months, respectively (hazard ratio for death, 0.66; 95% CI, 0.52-0.85; P <.001).
The prevalence of complete remission and composite complete remission were greater in the azacitidine-venetoclax group (P <.001 for both) compared with the placebo group. The results indicated that nausea of any grade was reported in 44% of those in the azacitidine-venetoclax arm and in 35% of patients in the placebo arm. Among those patients in the azacitidine-venetoclax and placebo groups, other adverse events included grade 3 or greater thrombocytopenia (45% and 38%, respectively), neutropenia (42% and 29%, respectively), and febrile neutropenia (42% and 19%, respectively). In addition, 85% of azacitidine-venetoclax group members and 67% of control group members had infections of any grade.
The authors noted, “The safety profile of azacitidine plus venetoclax was consistent with the known side effect profiles of both agents, and adverse events were consistent with expectations for an older AML population.” They also concluded, “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. Unlike monitoring of patients who receive azacitidine alone, ongoing attentiveness to the monitoring and management of myelosuppression is key for patient safety with this combination therapy.”
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