C090 | CAN SECONDARY ACUTE MYELOID LEUKEMIA IN ELDERLY PATIENTS REACH LONG-TERM SURVIVAL? A REAL-LIFE RETROSPECTIVE ANALYSIS BY THE RETE EMATOLOGICA LOMBARDA (REL)

Secondary acute myeloid leukemias (sAML), arising from antecedent hematologic disorders — such as myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN) — or therapy-related AML, are associated with a poor prognosis, particularly in elderly patients. Within the Rete Ematologica Lombarda (REL), we conducted a retrospective analysis of 349 patients (pts) aged ≥65 years diagnosed with sAML between 2020 and 2022. Among them, 212 (61%) received treatment with either chemotherapy (CT) or non-intensive therapy (niT: hypomethylating agents [HMA] with or without venetoclax [VEN]). We evaluated clinical and biological factors associated with overall survival (OS) in the treated cohort. The median age was 74 years (range, 65–88). AML was secondary to MDS in 53% of cases, to MPN in 28%, and therapy-related in 19%. Most pts had a Charlson Comorbidity Index (CCI) <2 (93%) and a performance status (PS) <2 (61%). According to SIE/SIES/GITMO criteria, 57% of pts were classified as unfit, 39% as fit, and 4% as frail. NiT was administered to 76% of pts (25% received HMA alone). Twenty-six (12%) pts underwent allogeneic stem cell transplantation (allo-SCT). Cytogenetic analysis showed an adverse karyotype in 48% of pts; TP53 mutations were detected in 12%. After a median follow-up of 25 months (m), the median OS in treated pts was 10 m. The majority of deaths were due to disease progression. OS was significantly superior in fit vs unfit pts (12.3 vs 8.1 m; p=0.013), in pts with PS <2 vs PS ≥2 (11.5 vs 4.7 m; p<0.001), in pts treated with CT vs niT (14 vs 8.6 m; p=0.011), in pts undergoing SCT vs no SCT (not reached vs 8.6 m; p<0.001), in pts without adverse cytogenetics (12.3 vs 7 m; p=0.001), and in pts without TP53 mutations (13.8 vs 6.6 m; p=0.001) (figure 1). No significant differences in OS were observed according to the type of secondary AML, CCI, or mutational status (NPM1, FLT3-ITD, splicing factor mutations, or epigenetic mutations). In multivariable analysis, only having a non-adverse karyotype (HR 0.29, CI 95% 0.15-0.58, p= 0.000) and undergoing SCT (HR 0.29, CI 95% 0.15-0.58, p= 0.000) predicted longer OS. In elderly pts with sAML receiving active treatment, prognosis is poor, and it is not independently influenced by most clinical and biological parameters, except for karyotype. However, 58% of the small subset of pts (12%) receiving allo-SCT achieved long-term survival.