C030 | GENOTYPE-PHENOTYPE CORRELATES AND OUTCOMES OF EXTRAMEDULLARY ACUTE MYELOID LEUKEMIA

Background: Genomic abnormalities associated with extramedullary (EM) acute myeloid leukemia (eAML) and their impact on clinical outcomes are not well understood since previous studies were limited to small case series with controversial results. Aim and methods: A large monocentric cohort of 600 newly diagnosed AML patients (pts) at the University of Florence (Careggi Hospital), comparing those with and without concurrent EM involvement, was analyzed. Results: 494 (82%) pts were treated with intensive chemotherapy (cht), and 243 (41%) with allogenic hematopoietic stem cell transplantation (AHSCT). Out of 539 evaluable pts, 245 (46%) had abnormal karyotype, 71 (13%) had a complex karyotype. 140 (23%) NPM1, 126 (21%) FLT3-ITD, 27 (5%) inv (16), 26 (4%) CEBPA bZIP, 24 (4%) t(8;21). Of the whole cohort, 103 pts (17%) had eAML, 81% and 19% (n=119) with de novo and sAML, respectively. eAML were younger (56 vs 58 years, p=0.01), with higher white blood cell (p< 0.01) and peripheral blast count (p= 0.02). ELN '22 favorable risk was less common in eAML (18% vs 31%, p=0.01), while the intermediate category was more frequent (42% vs 32%, p=0.03). FLT3-ITD (31% vs 19%, p<0.01) and TP53 mutations (22% vs 10%, p=0.04) were also more common in eAML. Median overall survival (OS) of the cohort was 20.2 months, significantly shortened in eAML (11 vs 23.5 months, p<0.01) (Fig. 1A). Of note, having more than 1 EM localization was associated with furtherly shortened OS (8.5 months, HR 2; p<0.01) (Fig. 1B). In multivariate analysis, eAML (HR 1.4; p=0.02), older age (p<0.01), and ELN '22 risk categorization (p<0.01) were significant for reduced OS. Considering eAML pts only, ELN '22 failed to resolve intermediate and adverse categories (p=0.4). Intensive cht and AHSCT were associated with superior survival in pts with and without eAML. For eAML, SRSF2 (HR 3; p=0.03), SETBP1 (HR 10; p=0.04), and JAK2 (HR 4.9; p=0.04) mutations were associated with reduced OS. When analyzing ELN '22 risk categories separately for pts with and without eAML, a significant different OS for intermediate risk pts only was documented (HR 1.6; p=0.02, Fig. 1C). Conclusions: The study establishes key molecular markers associated with EM, such as FLT3-ITD and TP53 mutations. Of interest, ELN '22 categorization lost the power to discriminate between intermediate and adverse category. Finally, intensive cht and AHSCT improved OS in pts with EM involvement.