P085 | ASXL1 MUTATIONS DETERMINE INFERIOR OUTCOME IN LOWER-RISK MYELODYSPLASTIC SYNDROMES:MONOCENTRIC REAL-LIFE DATA

The management of lower-risk myelodysplastic syndromes (LR-MDS), defined by IPSS-R as very low,low and intermediate-risk categories, is focused on the treatment of cytopenias, with the aim of improving quality of life and risk of disease progression. IPSS-molecular (M) has shown to provide better risk stratification, often classifying as high-risk patients (pt) who were defined as LR-MDS by IPSS-R. Mutations (mt) in additional sex combs like 1 (ASXL1) gene are associated with poor prognosis but it is currently unknown the impact of the presence and type of ASXL1 mts on the LR-MDS setting stratified by IPSS-R and IPSS-M. The objective of the study is to evaluate the prognostic impact of ASXL1 mt in pt with LR-MDS. Pt with MDS according to WHO 2022 (<5% bone marrow blasts) were stratified by both IPSS-R and IPSS-M. DNA from peripheral blood or bone marrow mononuclear cells were tested by NGS on a MiniSeq Platform with Custom Myeloid Solution. Bioinformatic analysis were performed using Sophia DDM Platform. 65 LR-MDS pt molecularly annotated were identified. According to WHO 2022, 6 pt were categorized as MDS-5q, 14 as MDS-SF3B1 and 45 as MDS-LB. Application of the IPSS-M helped to improve prognostic accuracy in 6 out of 65 pt classified as LR-MDS by IPSS-R: 2 pt were stratified as high-moderate and 4 as high-risk categories. ASXL1 mt was identified in 12 pt. Frameshift and nonsense mt of ASXL1 were equally distributed. The most frequent co-mt were: SRSF2 (n=5), TET2 (n=4) and DNMT3A (n=2). The presence of ASXL1 mt tended to associate with lower absolute neutrophil counts (p=0.06) but not with other parameters, such as age, sex, complete blood count, bone marrow blasts and karyotype. After a median follow-up of 43 months, 5 deaths and 3 leukemic transformations were observed in pt with ASXL1 mt, and 8 deaths and 3 leukemic transformations in the wild-type (wt) group. Notably, LR-MDS pt with ASXL1 mt had inferior OS compared to wt (median OS 51 months versus not reached; 95% CI 3.8-NR, p=0.025) (fig.1a). Similarly, ASXL1 mt adversely affected LFS (median LFS 63 months versus NR; 95% CI 3.6-NR, p=0.027) (fig.1b). In our analysis the type of ASXL1 mt had no impact on OS and EFS. These preliminary results show that the presence of ASXL1 mt adversely affects LFS and OS of LR-MDS stratified by IPSS-R and IPSS-M. Additional analyses on an expanded cohort will better clarify the independent impact of ASXL1 mt on disease outcome in this subgroup of pt.