Abstract
BACKGROUND: Octa-nonagenarians with acute myeloid leukemia (AML) represent a high-risk group due to frequently poor performance status, adverse genomics (e.g., TP53 mutations, complex karyotype), a high incidence of secondary AML, and inability to undergo an allogeneic stem cell transplantation. Evaluating their outcomes with modern treatment approaches is important. METHODS: This retrospective study analyzed outcomes of patients ≥80 years old with newly diagnosed AML treated at our center from 2013-2023. RESULTS: A total of 289 patients (median age, 83 years; range, 80-95 years) were included. Venetoclax containing low-intensity therapy was administered to 107 patients (37.0%). AML subtypes included de novo (123, 42.6%), secondary (114, 39.4% [82 treated-secondary, 32 untreated-secondary]), therapy-related without prior myeloid neoplasm (40, 13.8%), and post-myeloproliferative neoplasm AML (12, 4.3%). Composite complete response (CRc) was achieved in 43.2%, with higher rates in venetoclax-treated patients (61.7% vs. 32.4%, p < .001). Median relapse-free survival among patients with a CRc was 6.5 months. Median overall survival (OS) was 6.2 months; 13.7 months for those achieving CRc. One-year nonrelapse mortality was 18.4%. Median OS was 7.7 months with venetoclax versus 5.4 months without. In de novo AML, median OS with venetoclax was 11.1 months. Among venetoclax-treated patients, favorable subgroups (e.g., NPM1 and/or IDH1/2 mutations and/or myelodysplasia related mutations without TP53 mutation and adverse cytogenetics) achieved OS up to 16.0-16.3 months. On multivariate analysis, de novo AML, wild-type TP53, and venetoclax therapy were independently associated with improved OS. CONCLUSIONS: Low-intensity venetoclax-based regimens offer meaningful survival benefits in selected octa-nonagenarian patients with AML, particularly those with favorable genomic profiles.