DP018 | HYPOMETHYLATING AGENTS ALONE STILL HAVE A ROLE IN ACUTE MYELOID LEUKEMIA TREATMENT: RESULTS OF A RETROSPECTIVE REAL-LIFE STUDY ON 132 PATIENTS.

• Published in: Haematologica
• Main Authors: R. Palmieri, F. Pilo, M. Pettinau, G. Paterno, F. Mallegni, E. Meddi, F. Moretti, I. Cerroni, M.I. Del Principe, L. Maurillo, G. Caocci, A. Venditti
• Format: Article
• Language: English
• Published: Ferrata Storti Foundation 2025-09-01
• Online Access: https://haematologica.org/article/view/12782
• ISSN: 0390-6078; 1592-8721

Decitabine (DEC) and Azacitidine (AZA) alone or in combination with Venetoclax (VEN) represent the gold standard treatment for unfit patients (pts) with acute myeloid leukemia (AML). As these two strategies differ in terms of efficacy (greater with HMAs-VEN combination) and tolerability (better with HMAs monotherapy), how to select the most appropriate therapy option, avoiding over or under treatment, is still unclear. To clarify this issue, we compared the outcomes of pts receiving either HMAs-VEN combination or HMAs monotherapy in a real-world series of 132 pts from Tor Vergata Hospital of Rome and A.Businco' Hospital of Cagliari. Out of 132 pts, 73 (55.3%) received HMAs and 59 (44.7%) HMAs-VEN. The two groups didn’t differ in terms of sex, age, performance status (PS), AML Composite Model (AML CM) score, or ELN2022 disease risk distribution. As expected, significantly higher proportion of HMAs-VEN pts (45.7%) achieved complete remission (CR), as compared to HMAs ones (26%) (p=0.03). At a median follow up of 10 months (mos), median overall survival (OS) of the study cohort was 7.8 mos, with no differences between the two groups (8,9 mos vs. 6.6 mos for HMAs-VEN vs. HMAs, respectively; p=0.55). Irrespective of treatment received, median OS was proportioned to PS level (median OS of 9.8 mos, 11.3 mos, 5.4 mos, and 1.7 mos for ECOG PS 0, 1, 2, and 3-4, respectively; p=0.01) and to disease risk (median OS of 18.6 mos, 9.8 mos, and 4.7 mos for ELN2022 favorable, intermediate, and adverse, respectively; p=0.71). Univariate analysis showed an OS benefit of HMAs over HMAs-VEN in pts aged>75 years (Hazard Ratio [HR]=1.7;), or with PS 2 (HR=1.37). Conversely, in pts with ELN2022 adverse risk (HR=0.33), age<75 years (HR=0.61), AML CM 5-8 (HR=0.65), PS 0-1 (HR=0.66), Charlson index 0-4 (HR=0.69), or AML CM 0-4 (HR=0.71;), HMAs-VEN were beneficial over HMAs. Finally, for pts with AML CM>9 (HR=0.76), Charlson index>4 (HR0.85), ELN2022 intermediate risk (HR=0.91), and ELN2022 favorable risk (HR=1), no clear benefit of any of the two strategies was observed. [Figure 1] Even if HMAs/VEN represents the gold standard for the treatment of unfit AML patients, we identified specific parameters that seem to favor either HMAs (age>75 years and PS 2) or HMAs-VEN (age<75 years, AML CM 0-8, PS 0-1, Charlson Index 0-4, ELN2022 adverse risk). A prospective observation with an extended follow up is warranted to confirm these preliminary findings.