Efficacy
Azacitidine and venetoclax therapy is an effective and well-tolerated combination therapy for upfront treatment of elderly AML and has been found to be effective in AML with a variety of mutations. Following preclinical data suggesting synergistic activity between hypomethylating agents and venetoclax, a phase 1b study looked at the safety and preliminary efficacy of azacitidine/decitabine and venetoclax combination therapy in elderly patients over age 65, with previously untreated AML, featuring intermediate or poor risk cytogenetics, unsuitable for standard induction therapy.r
DiNardo et al.r confirmed the superiority of the azacitidine-venetoclax combination over azacitidine alone. The median duration of follow up was 20.5 months, OS was 14.7 months (95% confidence interval [CI], 11.9 to 18.7) compared to 9.6 months (95% CI, 7.4 to 12.7) and a statistically significant (p<0.001) better remission rate for the combination (hazard ratio (HR) for death, 0.66; 95% CI, 0.52 to 0.85; p<0.001). EFS was 9.8 months (95% CI, 8.4 to 11.8) in the combination group and 7.0 months (95% CI, 5.6 to 9.5) in the group receiving azacitidine alone (HR for disease relapse, treatment failure, relapse, or death, 0.63; 95% CI, 0.50 to 0.80; p<0.001). 36.7% of patients receiving combination therapy achieved CR, compared to 17.9% of the patients receiving azacitidine alone (p<0.001), duration of CR was 17.5 months (95% CI, 15.3 to NR) and 13.3 months (95% CI, 8.5 to 17.6). Treatment continued until disease progression or unacceptable toxicity. Patients receiving combination therapy received a median of 7 cycles, compared to 4.5 in the control group.
Figure 1: Overall survivalr
©NEJM 2020
Overall, this study and its predecessors provided evidence for an effective treatment for elderly AML patients.rrr