OBJECTIVES: The VIALE-A/C studies showed that venetoclax combination therapies improved overall survival (OS) and event-free survival (EFS) in patients with newly diagnosed acute myeloid leukemia (ND-AML) ineligible for intensive chemotherapy. The study aims to assess the long-term benefits of venetoclax+azacitidine (AZA)/low-dose cytarabine (LDAC) versus monotherapy AZA, LDAC, decitabine and best supportive care (BSC).

METHODS: A partitioned survival model with three health states (EFS, progressive/relapsed disease, and death) was developed to estimate the net health benefit in terms of life years (LYs) and quality-adjusted LYs (QALYs). OS, EFS, and remission rate were estimated using VIALE-A/C data for venetoclax+AZA/LDAC, AZA and LDAC. Efficacy inputs for decitabine and BSC were based on published literature. Best fitting parametric models were used to extrapolate efficacy outcomes for venetoclax+AZA/LDAC until year 5. Comparators’ efficacy was projected using parametric model or hazard ratio. Patients who had survived 5 years (base-case) or remained in EFS after 2 years (sensitivity) were considered cured and assumed to have the same mortality as the UK general population. Health-state utilities were estimated based on EQ-5D-5L from the same trials. Disutility associated with adverse events were considered. LYs and QALYs were aggregated over lifetime with 3.5% annual discount rate.

RESULTS: Over lifetime, venetoclax+AZA was associated with 20.7% cured patients and incremental LYs of 2.01, 1.96, 1.15 and 2.43 compared with AZA, LDAC, decitabine and BSC, respectively; the corresponding incremental QALYs were 1.48, 1.45, 0.85 and 1.78, respectively. Venetoclax+LDAC was associated with 8.6% cured patients and incremental LYs of 0.68 and 1.23 compared with LDAC and BSC, with incremental QALYs of 0.51 and 0.89, respectively. The sensitivity analysis results supported base-case findings.

CONCLUSIONS: Venetoclax+AZA/LDAC were projected to have much better long-term effectiveness compared to existing treatments over lifetime, and thus should be considered as alternative treatment options for ND-AML patients ineligible for intensive chemotherapy.