Comparative Safety and Effectiveness of Azacitidine plus Venetoclax versus Intensive Chemotherapy in Acute Myeloid Leukemia: A Propensity Score-Matched Analysis

INTRODUCTION: Azacitidine plus venetoclax (HMA&Ven) is a well-established treatment for acute myeloid leukemia (AML) in older or medically unfit patients, given its favorable efficacy and safety profile. Recently, there has been growing interest in extending its use to younger, fitter patients who are traditionally treated with intensive chemotherapy (IC). However, prior studies comparing HMA&Ven to IC have been limited by small sample sizes and inconclusive results. METHODS: We conducted a propensity score-matched cohort study using the TriNetX database to compare mortality and safety outcomes between HMA&Ven and IC in this population. We included patients aged 60-75 years with a diagnosis of AML who received either HMA&Ven or IC as induction therapy. Patients who underwent bone marrow transplantation or chimeric antigen receptor T-cell therapy following induction were excluded. We matched patients on predetermined variables, such as age, sex, race, comorbidities, medication, socioeconomic status, and healthcare utilization. RESULTS: The final analysis included 370 patients in each treatment group. At the 1-year follow-up, HMA&Ven demonstrated comparable all-cause mortality to IC (HR: 1.16 [95% CI: 0.93-1.44], p value = 0.186). However, HMA&Ven was associated with significantly lower rates of neutropenia (HR: 0.72 [95% CI: 0.60-0.87], p value <0.001) and sepsis (HR: 0.72 [95% CI: 0.56-0.92], p value = 0.009). CONCLUSION: Among AML patients aged 60-75, HMA&Ven showed similar 1-year all-cause mortality compared to IC, while offering a significantly better safety profile with reduced risks of neutropenia and sepsis.