What is myelodysplastic syndrome (MDS)?

From the Guidelines

Myelodysplastic syndrome (MDS) should be managed based on the subtype, risk category, and individual patient factors, with a focus on improving blood counts, delaying progression to acute myeloid leukemia (AML), and optimizing quality of life, as recommended by the most recent guidelines from the National Comprehensive Cancer Network (NCCN) 1.

Diagnosis and Classification

MDS is a group of blood disorders characterized by ineffective production of blood cells in the bone marrow, leading to low blood counts and increased risk of progression to AML. The diagnosis of MDS is based on blood and marrow examination, showing blood cytopenias, hypercellular marrow with dysplasia, with or without an excess of immature marrow cells (blasts) 1.

Treatment Options

Treatment options for MDS include:

• Supportive care with blood transfusions and growth factors like erythropoietin to stimulate blood cell production
• 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) to improve blood counts and delay progression to AML
• Allogeneic stem cell transplantation, which offers the only potential cure for eligible patients, especially younger ones with severe disease 1

Risk Stratification

Early diagnosis and appropriate risk stratification using systems like the International Prognostic Scoring System (IPSS) are crucial for optimal management of MDS. The IPSS takes into account the marrow blast percentage, number and extent of cytopenias, and cytogenetic abnormalities to predict the risk of progression to AML and overall survival 1.

Monitoring and Follow-up

Regular monitoring of blood counts is essential for all MDS patients to track disease progression and treatment response. This includes regular complete blood counts, bone marrow biopsies, and cytogenetic analysis to assess the effectiveness of treatment and adjust the management plan as needed 1.

From the FDA Drug Label

14 CLINICAL STUDIES 14.1 Myelodysplastic Syndromes (MDS)

Study 1 was a randomized, open-label, controlled trial carried out in 53 U. S sites compared the safety and efficacy of subcutaneous azacitidine for injection plus supportive care with supportive care alone (“observation”) in adult patients with any of the five FAB subtypes of myelodysplastic syndromes (MDS): refractory anemia (RA), RA with ringed sideroblasts (RARS), RA with excess blasts (RAEB), RAEB in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL)

Mylelodysplastic Syndrome is addressed in the context of a clinical study for azacitidine (SQ). The study included patients with various subtypes of myelodysplastic syndromes (MDS), including:

• Refractory anemia (RA)
• RA with ringed sideroblasts (RARS)
• RA with excess blasts (RAEB)
• RAEB in transformation (RAEB-T)
• Chronic myelomonocytic leukemia (CMMoL) The study compared the safety and efficacy of subcutaneous azacitidine for injection plus supportive care with supportive care alone in adult patients with these conditions 2.

From the Research

Myelodysplastic Syndrome Overview

• Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders with an inherent tendency for leukemic transformation 3.
• MDS is characterized by peripheral blood cytopenias, peripheral blood and bone marrow dysplasia/blasts, and clonal cytogenetic abnormalities 3.
• The diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy, with additional studies such as karyotype, flow cytometry, and molecular genetics providing complementary information 4.

Prognosis and Risk Stratification

• Prognosis of patients with MDS can be calculated using a number of scoring systems, including the Revised International Prognostic Scoring System (IPSS-R) 4.
• Somatic mutations, such as ASXL1, EZH2, or TP53 mutations, can help define prognosis and therapy 3.
• The IPSS-R system includes analysis of peripheral cytopenias, percentage of blasts in the bone marrow, and cytogenetic characteristics 4.

Treatment Options

• Currently, Food and Drug Administration (FDA)-approved drugs for the treatment of MDS are not curative and their effect on survival is limited; they include hypomethylating agents (HMA) azacitidine and decitabine, and lenalidomide for MDS with isolated del(5q) 3.
• Allogeneic stem cell transplant (ASCT) remains the only treatment option for possible cure 3, 5, 6.
• For non-transplant candidates, participation in clinical trials is preferred over conventional therapy 3.
• Novel therapeutics, such as luspatercept and the oral HMA ASTX727, have been approved in 2020 4.
• Other treatment options, such as growth factor support, lenalidomide, HMAs, intensive chemotherapy, and alloSCT, are available depending on the patient's risk, transfusion needs, and other factors 4.

Management of Anemia

• For patients with lower-risk MDS, one of the primary clinical goals is to alleviate the symptoms associated with anemia and minimize the transfusion burden 7.
• Supportive red blood cell (RBC) transfusions and erythropoiesis-stimulating agents (ESAs) may lead to clinical improvement, but frequent transfusions are often complicated by iron overload and decreased quality of life 7.
• Several additional therapeutics are available for symptomatic anemia in lower-risk MDS, including luspatercept, lenalidomide, and immunosuppressive therapy 7.
• Novel agents, such as imetelstat and roxadustat, are currently in development to address this area of clinical need 7.