P089 | COMPARATIVE ANALYSIS OF WHO 2022 MDS IB1 AND IB2 ENTITIES: A GROM-L STUDY.

Background: Classification of MDS with increased blast counts has been recently revised in ICC and WHO 2022 classifications. WHO 2022 has maintained the IB1 and IB2 categories , while the ICC introduced MDS/AML entity based on a 10% blast threshold. Recent genome studies on large MDS cohorts have confirmed prognostic role of blast %, thus questioning the ability of a fixed 10% blast threshold to identify different MDS entities. Our study aims at comparing the biological characteristics of MDS-IB1 and IB2 to identify distinguishing features. Methods: We investigated in a comparative fashion 34 MDS-IB1 and 26-IB2 defined according to WHO 2022 focusing on clinical, genetic data together with outcome collected within the GROM-L Italian cooperative group. Results: When comparing IB1 vs IB2 patients, no significant differences were observed in age and cytopenias, with only a tendency for lower Hb levels in IB2 vs. IB1 (8.8 vs 9.5 g/dL, p=0.1). In line, IB2 patients presented with higher rate of transfusion dependency. When comparing IB1 and IB2, cytogenetics disclosed normal karyo in 55% vs.61% (p= 0.79), high risk karyo in 22% vs. 11% (p=0.4). When stratified with IPSS-R, high/ very high risk were significantly more represented in IB2 vs. IB1 ( 35% vs. 80%, p=0.0006). Similarly, using IPSS-M higher risk categories were more represented in the IB2 vs IB1. NGS data showed ASXL1, SRFSF2, TET2, DNMT3A, TP53, Sf3B1, RUNX1,ZRZS2, CBL, NRAS, IDH2, IDH1 as the most recurrently mutated genes. Mean mutations per pt did not differ between IB1 and IB2 (2 vs 2.7p=0.4). A significant enrichment in IDH2 mutations was observed in IB2 vs IB1 (3/16 vs 0/26; p=0.05) together with signalling pathways mutations (NRAS, CBL) (4/15 vs 0/26; p=0.01). 16/34 IB1 patients underwent therapy with aza, 5 EPO, 4 Lena ,8 did not begin therapy. As to IB2, 21/26 were treated with Aza, 5 did not receive active therapy. Allo-SCT was performed in 4 patients (3 IB2 and 1 IB1). In the IB1 and IB2 cohorts, 6/34 (17%) and 4/26 (15%) evolved in AML, 7/34 (20%) and 5/26 (19%) patients died at a median follow-up of12.8 months. Conclusions: Our analysis highlights the biologic overlap of MDS-IB1 and IB2 in terms of karyotype, clinical characteristics, and outcome. However, IDH2 and proliferative pathways mutations were more represented in patients with >10% blasts. Despite the small patient size, our study suggest that specific mutations might direct in the identification of a higher-risk MDS profile.