Session: 637. Myelodysplastic Syndromes – Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, adult, elderly, Clinical Research, real-world evidence, Study Population, Human
Comparison of the genetic profiles of patients with different subtypes of MDS showed that patients with MDS-low blasts (LB) and those with MDS with LB and ring sideroblasts (RS) exhibited comparable mutation profiles, while patients with MDS-SF3B1 had different mutation pattern from that of these two subtypes. Among patients with MDS-increased blasts-1 (IB1), MDS-IB2 and MDS-f, patients with MDS-IB2 had higher frequencies of NRAS (9% vs. 2%, P=0.019) and mono-allelic TP53 (7% vs. 1%, P=0.031) mutations, and a trend of more TET2 (19% vs. 10%, P=0.059) mutations than those with MDS-IB1. In addition, patients with MDS-f exhibited lower incidence of TET2 (0% vs. 19%, P=0.020), and STAG2 mutations (8% vs. 27%, P=0.050) as compared to those with MDS-IB. Furthermore, patients with MDS-biTP53 had specific concurrent genetic alterations with few co-occurring mutations which differed from those found in patients with MDS-IB or MDS-f.
We performed pairwise survival comparisons among each subtypes of MDS (Figure 1). In low-risk MDS, patients with MDS-h had significantly longer median leukemia-free survival (LFS) and overall survival (OS) (185.5 months for median LFS and OS) compared with those with MDS-LB and RS [38.3 months for median LFS (P=0.013) and OS (P=0.010)], while had a similar outcome compared to those with MDS-LB [170.2 months for median LFS (P=0.152) and OS (P=0.146)], and MDS-SF3B1 [114.6 months for median LFS (P=0.549) and OS (P=0.528)]. For patients with increased blasts or biTP53 mutations, those with biTP53 inactivation had the worst outcomes (median LFS: 3.9 months and OS: 4.5 months, all P<0.001) compared to those with MDS-f (median LFS: 16.6 months and OS: 17.7 months), MDS-IB2 (median LFS: 10.0 months and OS: 17.7 months), and MDS-IB1 (median LFS: 25.6 months and OS: 31.4 months). Patients with MDS-f had similar survival to those with MDS-IB2 and IB-1 in terms of LFS (16.6 vs. 25.6 months, P=0.271) and OS (17.7 vs. 31.4 months, P=0.194) .
Multivariable analysis showed that IPSS-M (P<0.001), old age (HR for LFS: 1.023; for OS: 1.032, P<0.001), and the 2022 WHO categorization (P<0.001) could predict LFS and OS independently and that HSCT could improve LFS (HR, 0.492, P=0.001) (Table 1). Subgroup analysis of the impact of transplantation using time-dependent Cox regression revealed that allo-HSCT could prolong both LFS and OS in patients with MDS-IB1 (HR for LFS: 0.293, for OS: 0.350, P<0.001), LFS alone (HR: 0.534, P=0.049) in patients with MDS-IB2, and a trend of LFS (HR: 0.305, P=0.078) in patients with MDS-f. However, allo-HSCT failed to remedy the dismal outcomes for patients with MDS-biTP53.
In conclusion, based on the evidence gathered from this cohort analysis, the 2022 WHO classification promote efficient segregation of this heterogeneous disease, with focus on the differences in molecular features and prognoses across different disease subtypes, leading to accurate MDS diagnosis and effective risk-adapted treatment.
Disclosures: No relevant conflicts of interest to declare.
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