What is Myelodysplastic Syndrome (MDS)?

From the Guidelines

Myelodysplastic syndrome (MDS) patients should be treated based on risk stratification, with low-risk patients managed with supportive care and higher-risk patients requiring disease-modifying therapy, as recommended by the NCCN guidelines 1.

Overview of Myelodysplastic Syndrome

Myelodysplastic syndrome (MDS) is a group of bone marrow disorders characterized by ineffective blood cell production, leading to low blood counts and abnormal cell development. The diagnostic criteria for MDS continue to evolve, based on morphology, cytogenetics, and the presence of cytopenias, allowing for better treatment guidance 1.

Treatment Approaches

Treatment of MDS depends on risk stratification, with low-risk patients often managed with supportive care including transfusions and growth factors like erythropoietin. Higher-risk patients typically require disease-modifying therapy such as hypomethylating agents (azacitidine 75 mg/m² for 7 days every 28 days or decitabine 20 mg/m² for 5 days every 28 days) 1.

• Lenalidomide (10 mg daily) is specifically effective for patients with deletion 5q.
• Allogeneic stem cell transplantation remains the only potentially curative option for eligible patients, typically those younger than 75 with good performance status and higher-risk disease.

Monitoring and Complications

Regular monitoring includes complete blood counts every 1-3 months and bone marrow examinations as clinically indicated. The underlying pathophysiology involves genetic mutations affecting hematopoietic stem cells, leading to dysplasia and ineffective hematopoiesis. Patients should be monitored for complications including infections, bleeding, and progression to acute myeloid leukemia, which occurs in approximately 30% of cases 1.

Classification and Prognosis

The WHO classifications were revised to improve both the diagnostic and prognostic capabilities of these entities. MDS with del(5q) generally has a relatively good prognosis and is highly responsive to lenalidomide therapy. With a moderate degree of variability, patients with MDS-EB or MDS-EB-T generally have a relatively poor prognosis, with a median survival ranging from 5 to 12 months 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 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

Overview of Myelodysplastic Syndrome

• Myelodysplastic syndrome (MDS) is a disorder of hematopoietic stem cells characterized by ineffective hematopoiesis, leading to pancytopenia and an increased risk of infection or bleeding 3.
• MDS is classified according to World Health Organization criteria and the International Prognostic Scoring System, with patients divided into lower- and higher-risk categories 4, 5.
• The treatment of MDS begins with risk stratification using a validated tool such as the International Prognostic Scoring System (IPSS) or its revised version (IPSS-R) 6.

Diagnosis and Risk Stratification

• 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 5.
• Prognosis of patients with MDS can be calculated using a number of scoring systems, including the Revised International Prognostic Scoring System (IPSS-R) 5.
• Somatic mutations can help define prognosis and therapy, with certain mutations associated with specific treatment outcomes 5.

Treatment Options

• Supportive care remains the mainstay of therapy for lower-risk MDS, with goals of decreasing transfusion needs and transformation to higher-risk disease or acute myeloid leukemia (AML) 7, 4.
• Erythropoiesis-stimulating agents (ESAs) can be used to improve anemia in patients with lower-risk MDS and isolated anemia, no high-risk features, and endogenous erythropoietin (EPO) levels below 500 U/L 6.
• Specific therapies such as luspatercept, lenalidomide, and immunosuppressive therapy may be beneficial for certain patient subgroups 7, 6.
• Higher-risk MDS is typically treated with hypomethylating agents (HMAs) such as azacitidine or decitabine, with allogeneic hematopoietic stem cell transplantation (aHSCT) considered for eligible patients 4, 6.

Emerging Therapeutic Options

• Several novel agents are currently in development for the treatment of MDS, including imetelstat, roxadustat, and venetoclax 7, 6.
• Experimental agents such as myeloid cell leukemia 1 (MCL-1) inhibitors, eprenetapopt, and CPX-351 are also being investigated for the treatment of higher-risk MDS 6.
• Immunotherapies directed towards CD47, TIM3, or CD70, as well as interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors, pevonedistat, seclidemstat, and eltanexor, are also being explored as potential treatment options for MDS 6.