Treatment intensity in older adults with AML: Impact of age and induction regimen on remission and survival outcomes

Abstract Background: Treatment decisions in older adults with acute myeloid leukemia (AML) must balance disease biology with treatment tolerability. Low-intensity regimens such as Venetoclax with Azacitidine (Ven+Aza) are frequently used in older or frail patients, but their comparative effectiveness versus intensive chemotherapy remains uncertain. We investigated how age and induction intensity influence remission and overall survival (OS) in this population. Methods: We conducted a retrospective cohort study of 152 adult patients (age ≥18 years) diagnosed with AML at our institution between January 2010 and December 2024. Patients were excluded if they were <18 years of age or did not undergo AML-directed treatment. Patients were stratified by age (≤60 vs >60 years) and induction regimen (Anthracycline+Cytarabine [Anthra+Cyt] vs Venetoclax+Azacitidine [Ven+Aza]). Overall survival was assessed using Kaplan-Meier estimates and compared by log-rank testing. Multivariable Cox proportional hazards regression evaluated the impact of age, cytogenetic risk, and induction regimen on survival. Remission rates were assessed in patients >60 by treatment type. Results: Age Distribution: 50% (n=76) were aged >60 years. Overall Survival (OS): Age ≤60: Median OS not reached Age >60: Median OS 22.3 months (p=0.0058) Induction Regimen: Anthra+Cyt: Median OS not reached Ven+Aza: Median OS 19.2 months (p=0.003) Remission Rates in Patients >60: Anthra+Cyt: 68.97% Ven+Aza: 27.50% Multivariable Cox Model: Poor-risk cytogenetics: HR = 4.48, p = 0.0098 Age >60: HR = 1.91, p = 0.0734 (trend toward worse OS) Induction regimen: Not independently associated with OS Conclusions: In patients over 60 years old with AML, intensive induction therapy with Anthracycline+Cytarabine yields significantly higher remission rates and a trend toward improved overall survival compared to Venetoclax+Azacitidine. These results suggest that intensive therapy may benefit selected older adults who are fit enough to tolerate it. Age, cytogenetic risk, and induction regimen significantly influence overall survival in newly diagnosed AML patients. Older adults (>60 years) and those with poor-risk cytogenetics experience markedly worse outcomes. While intensive induction (Anthra+Cyt) was associated with superior survival compared to Ven+Aza, this difference may reflect underlying patient selection rather than treatment efficacy alone. The lack of significant impact from mutation status and intermediate-risk cytogenetics in multivariable analysis highlights the complexity of prognostication in AML. These findings underscore the need for personalized treatment strategies that integrate age, cytogenetic risk, and functional status. Future prospective studies should incorporate molecular profiling, comorbidity burden, and real-world treatment tolerability to optimize risk-adapted therapy—especially in older and therapy-related AML populations.