What is Myelodysplastic Syndrome (MDS)?

From the Guidelines

Myelodysplastic syndromes (MDS) should be managed based on risk stratification, with treatment options including supportive care, hypomethylating agents, and allogeneic stem cell transplantation, as outlined in the most recent guidelines 1. The management of MDS is complicated by the generally advanced age of the patients and the presence of nonhematologic comorbidities, which can affect treatment tolerance and outcomes 1. Key considerations in MDS management include:

• Risk stratification to guide treatment decisions
• Supportive care, including transfusions and growth factors like erythropoietin (EPO)
• Hypomethylating agents, such as azacitidine or decitabine, for higher-risk patients
• Allogeneic stem cell transplantation as a potentially curative option for eligible patients
• Iron chelation therapy with deferasirox for transfusion-dependent patients Regular monitoring is essential, with complete blood counts every 1-3 months and bone marrow evaluation if there's significant clinical change 1. The incidence of MDS increases with age, with approximately 4.5 cases per 100,000 people per year in the general population, and a higher incidence in individuals aged 70 and older 1. MDS develops due to genetic mutations in hematopoietic stem cells, leading to dysplastic changes and ineffective hematopoiesis, with a risk of progression to acute myeloid leukemia in approximately 30% of cases 1. The diagnosis and disease stratification of MDS are based on multiple factors, including clinical data, peripheral blood and bone marrow morphology, fluorescence in situ hybridization, cytogenetics, flow cytometry, and next-generation sequencing myeloid mutation panels 1. The major clinical morbidities associated with MDS are cytopenia-associated complications and the potential for MDS to evolve into acute myeloid leukemia (AML) 1. Chronic transfusions, treatment toxicity, and secondary phenomena such as systemic inflammatory conditions can increase the complexity of care for patients with MDS 1. The NCCN guidelines provide a framework for the diagnosis, risk stratification, and management of MDS, with the goal of improving patient outcomes and quality of life 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)

The drug label directly supports the use of azacitidine for the treatment of Myelodysplastic Syndromes (MDS), including the subtypes:

• Refractory anemia (RA)
• RA with ringed sideroblasts (RARS)
• RA with excess blasts (RAEB)
• RAEB in transformation (RAEB-T)
• Chronic myelomonocytic leukemia (CMMoL) 2

From the Research

Definition and Characteristics of MDS

• Myelodysplastic syndromes (MDS) are clonal hematopoietic malignancies that cause morphologic bone marrow dysplasia along with anemia, neutropenia, or thrombocytopenia 3
• MDS are associated with an increased risk of acute myeloid leukemia (AML) 3, 4, 5, 6, 7
• The yearly incidence of MDS is approximately 4 per 100 000 people in the United States and is higher among patients with advanced age 3

Risk Factors and Diagnosis

• Risk factors associated with MDS include older age and prior exposures to toxins such as chemotherapy or radiation therapy 3, 4, 7
• Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy 4, 5, 7
• Information obtained from additional studies such as karyotype, flow cytometry, or molecular genetics is usually complementary and may help refine diagnosis 4, 5, 7

Treatment and Management

• Therapy for MDS is selected based on risk, transfusion needs, percent of bone marrow blasts, and cytogenetic and mutational profiles 4, 5, 7
• Goals of therapy are different in lower-risk patients than in higher-risk individuals and in those with hypomethylating agent (HMA) failure 4, 5, 7
• Current available therapies include growth factor support, lenalidomide, HMAs, intensive chemotherapy, and allogeneic stem cell transplantation (alloSCT) 4, 5, 6, 7
• Novel therapeutics approved in 2020 are luspatercept and the oral HMA ASTX727 7

Prognosis and Survival

• The median age at diagnosis is approximately 70 years, and the yearly incidence rate increases to 25 per 100 000 in people aged 65 years and older 3
• Patients with lower-risk MDS have a median survival of approximately 3 to 10 years, whereas patients with higher-risk disease have a median survival of less than 3 years 3
• MDS are diagnosed in approximately 4 per 100 000 people in the United States and are associated with a 5-year survival rate of approximately 37% 3