Azacitidine-Venetoclax in Elderly and Unfit Acute Myeloid Leukemia: Real-World Outcomes Outside Clinical Trials.
- 1Division of Hematology, AOU Policlinico "G. Martino", Via Consolare Valeria 1, 98125 Messina, Italy.
- 2Department of Human Pathology in Adulthood and Childhood "Gaetano Barresi", University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy.
Abstract
Background: Azacitidine plus venetoclax (AZA+VEN) is the current standard first-line treatment for elderly or medically unfit patients with acute myeloid leukemia (AML). However, patients treated in real-world settings often differ from those enrolled in clinical trials due to frailty, comorbidities, secondary AML, and prior exposure to hypomethylating agents. Materials and Methods: We retrospectively analyzed 21 consecutive AML patients who received frontline AZA+VEN between October 2020 and May 2026. Patient fitness was assessed according to SIE/SIES/GITMO criteria. Data on treatment responses, toxicities, treatment modifications, survival outcomes, ELN 2022/2024 risk categories, and comorbidity burden, including HCT-CI and augmented HCT-CI scores, were collected. Results: Median age was 77.2 years, and 95.2% of patients were considered unfit for intensive chemotherapy. Secondary AML was observed in 42.9% of cases, including 23.8% arising from myelodysplastic syndromes (MDSs) previously treated with azacitidine. The overall response rate was 57.1% (12/21), with a composite complete remission (CR/CRi) rate of 42.9%. The median time to response was 1.8 months. Venetoclax schedule modifications were required in 66.7% of patients, while azacitidine dose/schedule reductions were necessary in 57.1%. The augmented HCT-CI was significantly associated with OS, supporting further investigation of its potential prognostic value in this setting. Conclusions: AZA+VEN demonstrated meaningful clinical activity and manageable toxicity in elderly or unfit AML patients. Frailty and comorbidity burden had a substantial impact on outcomes, supporting the integration of biological and fitness-based risk assessment in the management of AML in real-world clinical practice.
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BibTeX
@article{fazio2026azacitidinevenetoclax,
title = {{Azacitidine-Venetoclax in Elderly and Unfit Acute Myeloid Leukemia: Real-World Outcomes Outside Clinical Trials.}},
author = {Manlio Fazio and Demetrio Gabriele Gerace and Giuseppe Mirabile and Rossana Leanza and Giuseppa Penna and Patricia Rizzotti and Sabina Russo and Adele Bottaro and Maria Elisa Nasso and Noemi Di Martino and Fabio Stagno and Alessandro Allegra},
journal = {Hematology reports},
year = {2026},
month = sep,
doi = {10.3390/hematolrep18050073},
url = {https://europepmc.org/article/MED/42931037},
note = {CC BY},
}
RIS
TY - JOUR
TI - Azacitidine-Venetoclax in Elderly and Unfit Acute Myeloid Leukemia: Real-World Outcomes Outside Clinical Trials.
AU - Manlio Fazio
AU - Demetrio Gabriele Gerace
AU - Giuseppe Mirabile
AU - Rossana Leanza
AU - Giuseppa Penna
AU - Patricia Rizzotti
AU - Sabina Russo
AU - Adele Bottaro
AU - Maria Elisa Nasso
AU - Noemi Di Martino
AU - Fabio Stagno
AU - Alessandro Allegra
PY - 2026
DA - 2026/09/30
JO - Hematology reports
DO - 10.3390/hematolrep18050073
UR - https://europepmc.org/article/MED/42931037
AB - Background: Azacitidine plus venetoclax (AZA+VEN) is the current standard first-line treatment for elderly or medically unfit patients with acute myeloid leukemia (AML). However, patients treated in real-world settings often differ from those enrolled in clinical trials due to frailty, comorbidities, secondary AML, and prior exposure to hypomethylating agents. Materials and Methods: We retrospectively analyzed 21 consecutive AML patients who received frontline AZA+VEN between October 2020 and May 2026. Patient fitness was assessed according to SIE/SIES/GITMO criteria. Data on treatment responses, toxicities, treatment modifications, survival outcomes, ELN 2022/2024 risk categories, and comorbidity burden, including HCT-CI and augmented HCT-CI scores, were collected. Results: Median age was 77.2 years, and 95.2% of patients were considered unfit for intensive chemotherapy. Secondary AML was observed in 42.9% of cases, including 23.8% arising from myelodysplastic syndromes (MDSs) previously treated with azacitidine. The overall response rate was 57.1% (12/21), with a composite complete remission (CR/CRi) rate of 42.9%. The median time to response was 1.8 months. Venetoclax schedule modifications were required in 66.7% of patients, while azacitidine dose/schedule reductions were necessary in 57.1%. The augmented HCT-CI was significantly associated with OS, supporting further investigation of its potential prognostic value in this setting. Conclusions: AZA+VEN demonstrated meaningful clinical activity and manageable toxicity in elderly or unfit AML patients. Frailty and comorbidity burden had a substantial impact on outcomes, supporting the integration of biological and fitness-based risk assessment in the management of AML in real-world clinical practice.
SN - 2038-8322
SN - 2038-8330
ER -