Comparative safety and effectiveness of azacitidine plus venetoclax versus intensive chemotherapy in acute myeloid leukemia: A propensity score-matched analysis.

Abstract

e18509 Background: Azacitidine combined with Venetoclax (HMA&Ven) has been widely used to treat acute myeloid leukemia (AML) in patients over 75 or those with comorbidities that preclude intensive chemotherapy (IC), due to its demonstrated efficacy and safety profile in this patient population. There has been increasing interest in expanding its use to young and less frail patients who would otherwise receive IC. However, no randomized trials have directly compared the effectiveness of HMA&Ven to IC in such patients. Given its potential for comparable outcome with reduced toxicity, we leverage a global database to compare the safety and efficacy of HMA&Ven and IC in patients with AML. Methods: We conducted a retrospective, propensity score-matched cohort study using the TriNetX database, including patients aged 60–75 years with AML who received HMA&Ven or IC induction therapy between 10/16/2020 and 11/30/2023. Patients undergoing bone marrow transplantation or chimeric antigen receptor T-cell therapy post-induction were excluded. The index date was the initiation of induction therapy. The primary outcome was 1-year all-cause mortality, with secondary outcomes including the 1-year incidence of adverse events such as neutropenia, sepsis, and others. Results: Among 1,301 eligible patients, 366 treated with HMA&Ven were matched to IC recipients based on baseline characteristics, comorbidities, medications and socioeconomic status with genetic mutations and cytogenetic abnormalities unadjusted due to underreporting. Cox analysis showed no significant difference in all-cause mortality (HR: 1.15, 95% CI: 0.93–1.41). However, compared to the IC cohort, HMA&Ven cohort had a lower risk of neutropenia (p=0.001), neutropenic fever (p<0.001), sepsis (p=0.022), bacteremia (p=0.010), and dermatitis (p=0.002). Tumor lysis syndrome, heart failure, and myocardial infarction rates were similar between groups. Conclusions: In AML patients aged 60–75 years, HMA&Ven demonstrated comparable all-cause mortality to IC and significantly lower risk of several adverse events including neutropenia, neutropenic fever, sepsis, bacteremia, and dermatitis. The incidence of tumor lysis syndrome, heart failure, and myocardial infarction was similar between the two groups. Outcomes HMA&Ven cohort IC cohort HR (95% CI) P-value At risk Cases At risk Cases All-cause mortality 366 194 366 174 1.15 (0.93-1.41) 0.190 Neutropenia 366 203 366 233 0.72 (0.60-0.87) 0.001 Neutropenic fever 366 171 366 220 0.61 (0.50-0.75) <0.001 Sepsis 366 111 366 139 0.75 (0.58-0.96) 0.022 Bacteremia 366 70 366 106 0.68 (0.51-0.91) 0.010 Tumor lysis syndrome 366 36 366 33 1.13 (0.70-1.81) 0.612 Dermatitis 366 54 366 86 0.59 (0.42-0.83) 0.002 Incident heart failure 316 40 328 41 0.99 (0.64-1.53) 0.959 Acute myocardial infarction 366 27 366 24 1.14 (0.66-1.98) 0.641