Long‐term follow‐up of VIALE‐A: Venetoclax and azacitidine in chemotherapy‐ineligible untreated acute myeloid leukemia

Abstract Venetoclax‐azacitidine is approved for treatment of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy based on the interim overall survival (OS) analysis of the VIALE‐A study (NCT02993523). Here, long‐term follow‐up is presented to address survival benefit and long‐term outcomes with venetoclax‐azacitidine. Patients with newly diagnosed AML who were ineligible for intensive chemotherapy were randomized 2:1 to receive venetoclax‐azacitidine or placebo‐azacitidine. OS was the primary endpoint; complete remission with/without blood count recovery (CR/CRi) was a key secondary endpoint. This final analysis was conducted when 100% of the predefined 360 OS events occurred. In VIALE‐A, 431 patients were enrolled to venetoclax‐azacitidine ( n = 286) or placebo‐azacitidine ( n = 145). At 43.2 months median follow‐up, median OS was 14.7 months (95% confidence interval [CI], 12.1–18.7) with venetoclax‐azacitidine, and 9.6 months (95% CI, 7.4–12.7) with placebo‐azacitidine (hazard ratio, 0.58 [95% CI, 0.47–0.72], p < .001); the estimated 24‐month OS rate was 37.5% and 16.9%, respectively. Median OS for patients with IDH1/2 mutations and those with measurable residual disease responses was reached in this final analysis. CR/CRi rate was similar to interim analysis. Any‐grade hematologic and gastrointestinal adverse events were most common in venetoclax‐azacitidine and placebo‐azacitidine arms, including thrombocytopenia (47% and 42%) and neutropenia (43% and 29%). No new safety signals were identified. Long‐term efficacy and safety confirm venetoclax‐azacitidine is an improvement in standard‐of‐care for patients with AML who are not eligible for intensive chemotherapy because of advanced age or comorbidities.