What is Myelodysplastic Syndrome (MDS)?

From the Guidelines

Myelodysplastic syndrome (MDS) patients should be managed with a risk-adapted approach, considering the most recent guidelines from 2017, which emphasize the importance of supportive care, including transfusions and growth factors, for low-risk patients, while higher-risk patients may require disease-modifying therapy with hypomethylating agents or allogeneic hematopoietic stem cell transplantation 1.

Overview of MDS

MDS is a group of bone marrow disorders characterized by ineffective blood cell production, leading to low blood counts and abnormal cell development. The development of secondary iron overload in MDS patients requiring regular red cell transfusions significantly worsens their survival, with a 30% increase in hazard for every 500 ng/mL of increase in serum ferritin above the threshold of 1,000 ng/mL 1.

Risk Stratification and Treatment

Treatment depends on risk stratification, with low-risk patients often managed with supportive care, including transfusions and growth factors like erythropoiesis-stimulating agents (ESAs) at doses of 40,000-60,000 units weekly. Higher-risk patients typically require disease-modifying therapy with 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) 1.

• Key considerations in managing MDS include:
  • Regular monitoring of blood counts
  • Transfusion support as needed to maintain hemoglobin above 7-8 g/dL and platelets above 10,000/μL
  • Management of iron overload with chelation therapy for patients requiring regular transfusions
  • Consideration of allogeneic hematopoietic stem cell transplantation for eligible higher-risk patients

Importance of Recent Guidelines

The most recent guidelines from 2017 emphasize the importance of a risk-adapted approach to managing MDS, considering factors such as age, performance status, and comorbidities when making treatment decisions 1. These guidelines also highlight the need for regular monitoring of blood counts and transfusion support as needed to maintain adequate blood cell counts.

Quality of Life and Survival

Preserving the MDS patient's quality of life (QoL) is a key goal of treatment, with management of anemia-related symptoms and comorbidities essential to maintaining QoL 1. The development of secondary iron overload can significantly worsen survival, emphasizing the importance of managing iron overload with chelation therapy for patients requiring regular transfusions.

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 azacitidine drug is used to treat 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) 2

From the Research

Definition and Characteristics of Myelodysplastic Syndrome

• Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML) 3, 4.
• MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy 3, 4.
• Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy 3, 4.

Risk Stratification and Prognosis

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

Treatment and Management

• Therapy 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) 4.
• Goals of therapy are different in lower-risk patients than in higher-risk individuals and in those with HMA failure 4.
• Current available therapies include growth factor support, lenalidomide, HMAs, intensive chemotherapy, and alloSCT 3, 4.
• Novel therapeutics approved in 2020 are luspatercept and the oral HMA ASTX727 4.
• For patients with lower-risk MDS, options include lenalidomide, immunosuppressive therapy, and novel agents such as imetelstat and roxadustat 5, 6.
• For patients with higher-risk MDS, options include azacitidine, decitabine, and intensive chemotherapy 3, 6.

Anemia Management

• Anemia is a common symptom in patients with MDS, and management options include supportive red blood cell (RBC) transfusions, erythropoiesis-stimulating agents (ESAs), and novel therapeutics such as luspatercept 5.
• Frequent transfusions can lead to iron overload and decreased quality of life, highlighting the need for alternative therapeutic options 5.