# The Effectiveness of Hypomethylating Agents in Elderly Patients With Acute Myeloid Leukemia: Insights From a Single-Center Experience

## TL;DR

This study shows that combining hypomethylating agents with Venetoclax improves survival in elderly patients with acute myeloid leukemia.

## Contribution

The study provides new evidence on the effectiveness of combining hypomethylating agents with Venetoclax in elderly AML patients.

## Key findings

- Patients treated with Venetoclax in second-line therapy had a median overall survival of 11 months, compared to 7 months with single-line therapy.
- Venetoclax-treated patients showed significantly higher transfusion independence.
- The survival difference reached statistical significance (p = 0.038).

## Abstract

Introduction: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy mainly affecting older adults. It presents significant challenges due to unfavorable cytogenetic characteristics and associated comorbidities, which restrict treatment options. Addressing these complexities is essential for improving patient outcomes. Hypomethylating agents (HMAs) such as azacitidine (AZA) and decitabine (DAC) are standard treatments for elderly patients unfit for intensive chemotherapy. The introduction of Venetoclax (Ven), a selective BCL-2 inhibitor, has shown promise in improving treatment outcomes.

Methods: A retrospective analysis was conducted on 82 elderly AML patients treated at the Coltea Clinical Hospital, Bucharest, Romania, between January 2017 and December 2023. Patients received non-intensive chemotherapy with either AZA, DAC, LDAC, or their combination with Venetoclax. Clinical, cytogenetic, and molecular parameters were documented, and survival outcomes were analyzed using the Kaplan-Meier method. Statistical significance was assessed using the log-rank test and Cox proportional hazard regression.

Results: The median overall survival (OS) was seven months among the patients receiving a single line of therapy. By contrast, in those treated with a second-line regimen that included Venetoclax, OS increased to 11 months. Although the sample size was small, this difference reached statistical significance (p = 0.038). Transfusion independence was significantly higher in Venetoclax-treated patients.

Conclusion: Hypomethylating agents, in combination with Venetoclax, have emerged as the standard of care for elderly patients with AML, offering superior survival and response rates. Nevertheless, further therapeutic advancements are crucial to enhance treatment outcomes in this population.