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1878 Clinico-Genetic and Prognostic Analyses of 635 Patients with Myelodysplastic Neoplasms Based on the 2022 World Health Organization Classification

Program: Oral and Poster Abstracts
Session: 637. Myelodysplastic Syndromes – Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, adult, elderly, Clinical Research, real-world evidence, Study Population, Human
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Hsin-Yu Lu1*, Wan Hsuan Lee1,2,3*, Chien-Chin Lin, MD, PhD1,4*, Cheng-Hong Tsai, MD1,5*, Feng-Ming Tien1,3*, Min Yen Lo, MD1,3,6*, Mei-Hsuan Tseng7*, Yuan-Yeh Kuo7*, Shan-Chi Yu8*, Ming-Chih Liu8*, Chang-Tsu Yuan, MD9*, Yi-Tsung Yang1,2,3*, Ming-Kai Chuang, MD1,4*, Jih-Luh Tang, MD1,10, Hsun-I Sun, MD7*, Yi-Kuang Chuang7*, Hsin-An Hou, M.D.; Ph.D.1, Hwei-Fang Tien, MD, PhD1,11 and Wen-Chien Chou, MD, PhD1,4

1Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
2Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan
3Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
4Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
5Department of Medical Education and Research, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
6Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
7Tai-Chen Cell Therapy Center, National Taiwan University, Taipei, Taiwan
8Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
9Department of Pathology, National Taiwan University Hospital Cancer Center Branch, Taipei, Taiwan
10National Taiwan University Hospital Cancer Center Branch, Taipei, Taiwan
11Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei, Taiwan

Myelodysplastic neoplasms (MDS) are a heterogeneous group of clonal myeloid neoplasms characterized by dysregulated hematopoiesis. In the past several years, major advances in molecular technologies and the development of next generation sequencing have deepened our understanding of MDS pathobiology. Revisions of the existing classification were warranted. Under the aegis of the International Agency for Research on Cancer, the 2022 World Health Organization (WHO) classification was released. The 2022 WHO proposed new categories including MDS with biallelic TP53 inactivation (MDS-biTP53), MDS, hypoplastic (MDS-h) and MDS with fibrosis (MDS-f). In addition, the novel risk scoring system-Molecular International Prognostic Scoring System (IPSS-M) has been established. There are limited data that explore the application of the 2022 WHO classification of MDS in light of the IPSS-M. In this study, a cohort of 635 patients diagnosed as having primary MDS based on the 2022 WHO criteria was retrospectively reviewed. We aimed to elucidate the differences in genetic features and clinical outcomes among patients with different MDS subtypes, based on the 2022 WHO classification. The survival impact of allogeneic hematopoietic stem cell transplantation (allo-HSCT) was also evaluated. TruSight myeloid sequencing panel and the HiSeq platform were used to analyze the alterations of 54 myeloid neoplasm-relevant genes.

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.

*signifies non-member of ASH