What are the higher risk features of Myelodysplastic Syndromes (MDS)?

From the Guidelines

Higher risk myelodysplastic syndrome (MDS) features include a blast percentage greater than 10% in the bone marrow, complex cytogenetic abnormalities, multiple cytopenias, and high-risk genetic mutations, with the Revised International Prognostic Scoring System (IPSS-R) classifying patients with scores above 4.5 as high or very high risk, and treatment often includes hypomethylating agents like azacitidine or decitabine, with consideration for allogeneic stem cell transplantation in eligible patients, as recommended by the most recent guidelines 1.

Key Characteristics of Higher Risk MDS

• Blast percentage greater than 10% in the bone marrow
• Complex cytogenetic abnormalities, particularly those involving chromosomes 5,7, and 17
• Multiple cytopenias, defined as low blood counts affecting multiple cell lines
• High-risk genetic mutations, such as TP53, ASXL1, RUNX1, and EZH2

Prognostic Scoring Systems

• The Revised International Prognostic Scoring System (IPSS-R) classifies patients with scores above 4.5 as high or very high risk, with a shorter time to leukemic transformation and reduced overall survival compared to lower-risk MDS patients 1
• The IPSS-R is used to stratify patients into five risk groups, with clear differences in overall survival and risk of progression to acute myeloid leukemia (AML) 1

Treatment Options

• Hypomethylating agents, such as azacitidine (75 mg/m² for 7 days every 28 days) or decitabine (20 mg/m² for 5 days every 28 days), are commonly used to treat higher-risk MDS, with consideration for allogeneic stem cell transplantation in eligible patients 1
• Allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative treatment for higher-risk MDS patients, but its major obstacle is age, with most MDS patients being over 70 years old 1
• The decision to use reduced-intensity conditioning (RIC) or myeloablative approaches for allo-SCT is often disputed, with the relapse risk seeming to be higher in patients receiving RIC 1

From the FDA Drug Label

IPSS Classification n (%) Intermediate-1 Intermediate-2 High Risk 28 (31) 38 (43) 23 (26) The higher risk MDS features include High Risk classification, with 23 (26%) of patients having this classification 2.

• Key features of higher risk MDS include:
  • IPSS Classification: High Risk
  • Percentage of patients: 23 (26%)
  • FAB Classification: RAEB, RAEB-t, which are associated with higher risk MDS 2.

From the Research

Higher Risk MDS Features

• Higher risk myelodysplastic syndromes (MDS) are characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML) 3
• The Revised International Prognostic Scoring System (IPSS-R) is the most commonly accepted system for calculating prognosis in MDS patients, and it includes analysis of peripheral cytopenias, percentage of blasts in the bone marrow, and cytogenetic characteristics 3
• Somatic mutations can help define prognosis and therapy in higher risk MDS patients 3
• Therapy for higher risk MDS is selected based on risk, transfusion needs, percent of bone marrow blasts, cytogenetic and mutational profiles, comorbidities, potential for allogeneic stem cell transplantation (alloSCT), and prior exposure to hypomethylating agents (HMA) 3
• Goals of therapy in higher risk MDS are to prolong survival, and current available therapies include growth factor support, lenalidomide, HMAs, intensive chemotherapy, and alloSCT 3

Treatment Options for Higher Risk MDS

• Low-dose decitabine plus venetoclax has been shown to be safe and effective as post-transplant maintenance therapy for high-risk AML and MDS patients, with a 2-year overall survival (OS) rate of 85.2% and a 2-year event-free survival (EFS) rate of 84.7% 4
• Low-dose decitabine as part of a modified Busulfan-Cyclophosphamide (Bu-Cy) conditioning regimen has been shown to improve survival in AML patients with active disease undergoing allo-HSCT, with a 2-year OS rate of 80.7% and a 2-year leukemia-free survival (LFS) rate of 64.9% 5
• Azacitidine has been used as a salvage treatment for AML and MDS relapsing after allo-HSCT, with a median overall survival of 5.9 months and 9.5 months in two different patient groups 6
• Azacitidine and donor lymphocytes infusions (DLI) have been shown to be effective in treating AML and MDS relapsing after HSCT from alternative donors, with an overall response rate (ORR) of 49% and a complete response (CR) rate of 38% 7