Faculty, Staff and Student Publications

Publication Date

8-15-2025

Journal

Cancer

DOI

10.1002/cncr.70028

PMID

40772501

PMCID

PMC12329781

PubMedCentral® Posted Date

8-7-2025

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Humans, Leukemia, Myeloid, Acute, Male, Female, Aged, 80 and over, Retrospective Studies, Sulfonamides, Nucleophosmin, Bridged Bicyclo Compounds, Heterocyclic, Mutation, Treatment Outcome, Tumor Suppressor Protein p53, Antineoplastic Combined Chemotherapy Protocols, AML, hypomethylating agents, MRD, octa‐nonagenarian, venetoclax

Published Open-Access

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