DP094 | COMPARING TREATMENT OUTCOMES IN DE NOVO AND SECONDARY AML PATIENTS RECEIVING VENETOCLAX AND HYPOMETHYLATING AGENTS AS FIRST-LINE THERAPY: A MULTICENTER RETROSPECTIVE STUDY

Secondary AML (sAML), defined by a history of antecedent myelodysplastic (MDS) or myeloproliferative (MPN) disease,or presence of MDS-related gene mutations or cytogenetic abnormalities, has a worse prognosis than de novo AML (dnAML) in patients (pts) receiving intensive therapies. Data on sAML outcomes in pts treated with non-intensive regimens are limited. In this retrospective multicenter study, we compared outcomes, response rates and duration in dnAML and sAML pts treated frontline with HMA-VEN (≥1 cycle). Among 177 newly diagnosed AML pts, 93(53%) had dnAML and 84 (47%) sAML. Among sAML patients, 50 (60%) had a history of MDS (10 previously treated with azacitidine), 10 pts (12%) had blast-phase MPN, and 24 (28%) had MDS-related cytogenetic alterations (n=16) or gene mutations (n=8). Median age at diagnosis was 75 years (range 26–87) for dnAML and 73 (range 42–85) for sAML (p=0.08). Adverse cytogenetics were reported in 13% of dnAML (n=12/72) and 54% of sAML (n=43/80). Of 28 adverse-risk cytogenetic pts assessed for TP53 status, 7/9 dnAML and 8/19 sAML had mutations. The median number of cycles was 5 for dnAML (range 1–50) and 3.5 for sAML (range 1–54). With a median follow-up of 23 months (range 0.1–60), median overall survival (OS) was significantly lower in sAML than dnAML (10 months, 95% CI 7.6–13.1 vs 16 months, 95% CI 12.4–20.6; p=0.01). Among 150 evaluable pts, the composite complete remission rate (CR+CRi) was similar between groups (93% vs 82%, p=0.5), but responses were more durable in dnAML [median relapse-free survival (RFS) 18 months vs 9 months for sAML; p=0.01, Figure 1]. Overall, 13 pts (7%) underwent allogeneic transplantation (5 dnAML, 8 sAML). Non-adverse cytogenetics predicted better OS only in dnAML (median OS: 22 vs 10 months in sAML; p=0.005), while no survival difference was observed in dnAML and sAML pts with adverse cytogenetics (median OS: 11 vs 9 months; p=0.9). On multivariate analysis, adverse cytogenetics (HR 1.6, 95% CI 1.02–2.5; p=0.04) and sAML status (HR 1.9, 95% CI 1.2–2.9; p=0.005) were independently associated with worse survival. Among 77 patients with available next-generation sequencing (NGS) data, stratified by ELN 2024 risk classification, sAML pts showed a trend toward worse outcomes across all risk groups, although not statistically significant. Despite the effectiveness of HMA-VEN in both groups, sAML pts exhibit shorter response duration and poorer survival, underscoring the need for tailored approaches.