Should azacitidine and venetoclax be used to treat older patients with acute myeloid leukemia?

This trial was carried out to assess the effectiveness of azacitidine (Vidaza) in combination with venetoclax (Venclexta) for the treatment of untreated acute myeloid leukemia (AML) in older adults. The authors concluded that this combination prolonged survival and induced more remissions in these patients.

AML is a type of cancer that forms from a type of blood cell called a myeloid cell. AML progresses rapidly and commonly has a poor prognosis if left untreated. This is particularly true in older patients. Many older patients cannon undergo intensive chemotherapy due to risks of toxicity to normal tissues.

Azacitidine is a chemotherapy medication that switches off genes that help cancer cells grow and multiply. Ventoclax is a targeted therapy medication used in the treatment of AML. It targets a protein on cancer cells and promotes cancer cell death. Previous studies have shown that azacitidine in combination with venetoclax could be effective in treating AML in older patients who cannot undergo intensive chemotherapy. However, data from bigger trials are lacking.

There were 431 patients in this trial. The average age of patients was 76 years. Patients were randomly assigned to receive azacitidine and venetoclax (AV group) or azacitidine and placebo (AP group). The average follow-up for this study was 20.5 months. 

The average overall survival (OS) was 14.7 months in the AV group compared to 9.6 months in the AP group. The addition of venetoclax was associated with a 36% lower risk of death compared to placebo.

Significantly more patients in the AV group went into complete remission (primary disease is no longer active) compared to the AP group (36.7% vs. 17.9%). This was the same with patients who entered remission without full blood cell function restored (66.4% in the AV group vs. 28.3% in the AP group). 

Side effects including nausea occurred in 44% of the AV group and in 35% of the AP group. Low platelet (blood cells involved in clotting) was r ported in 45% of the AV group and in 38% of the AP group. There was an 85% rate of infections occurring in the AV group compared to 67% in the AP group.

The authors concluded that in patients with untreated AML who are ineligible for intensive chemotherapy, azacitidine plus venetoclax improved survival and induced more remissions compared to azacitidine alone.

This study was supported by AbbVie and Genentech, the manufacturers of venetoclax.