What is the treatment for myelodysplastic syndrome (MDS)?

Treatment of Myelodysplastic Syndrome

The treatment for myelodysplastic syndrome (MDS) should be risk-stratified based on the Revised International Prognostic Scoring System (IPSS-R), with hypomethylating agents (HMAs) like azacitidine being the standard of care for higher-risk MDS, while lower-risk MDS treatment focuses on managing cytopenias with erythropoiesis-stimulating agents, lenalidomide, or luspatercept. 1

Risk Stratification

Risk stratification is essential for determining the appropriate treatment approach:

• IPSS-R Categories:

  • Very low/Low risk: Median survival 5.3-8.8 years
  • Intermediate risk: Median survival 3.0 years
  • High/Very high risk: Median survival 0.8-1.6 years 2

• Risk factors considered:

  • Cytogenetic abnormalities
  • Bone marrow blast percentage
  • Hemoglobin level
  • Platelet count
  • Absolute neutrophil count 1

Treatment Algorithm for MDS

Lower-Risk MDS (IPSS-R Very Low, Low, Intermediate)

1. Anemia management:

   • Erythropoiesis-stimulating agents (ESAs) ± G-CSF

     • First-line for patients with serum erythropoietin <500 U/L
     • Response rate: 40-60% 1

   • Lenalidomide

     • First-line for patients with del(5q)
     • Response rate: 60-65% 1

   • Luspatercept

     • For patients with ring sideroblasts (MDS-RS) or SF3B1 mutation 1

   • Immunosuppressive therapy (ATG ± cyclosporine)

     • For younger patients (<65 years) who failed ESA treatment
     • Response rate: 25-40% 1

2. If failing above options:

   • Hypomethylating agents (HMAs)
     • Response rate: 30-40% 1

Higher-Risk MDS (IPSS-R High, Very High)

1. Allogeneic stem cell transplantation (Allo-HSCT)

   • Only potentially curative option
   • Consider for eligible patients ≤70 years with available donor 1

2. If not eligible for transplantation:

   • Azacitidine

     • Standard of care
     • Recommended over decitabine due to demonstrated survival advantage over conventional care regimens 2
     • Dosage: 75 mg/m²/day subcutaneously for 7 days every 28 days
     • Minimum 6 courses recommended to properly evaluate efficacy 2

   • Decitabine

     • Alternative HMA option
     • Dosage options:
       • Three-day regimen: 15 mg/m² by continuous IV infusion over 3 hours repeated every 8 hours for 3 days, cycle every 6 weeks
       • Five-day regimen: 20 mg/m² by continuous IV infusion over 1 hour daily for 5 days, cycle every 4 weeks 3

Supportive Care

• Red blood cell transfusions

  • For symptomatic anemia
  • Recommended hemoglobin threshold: at least 8 g/dL (9-10 g/dL with comorbidities) 1

• Platelet transfusions

  • For thrombocytopenia with bleeding or high bleeding risk

• Antibiotics

  • For infections in neutropenic patients

• Iron chelation therapy

  • For heavily transfused patients
  • Goal: decrease ferritin levels to <1000 mcg/L 1

Response Assessment

• Response criteria based on International Working Group (IWG) 2006 recommendations:

  • Complete remission (CR)
  • Partial remission (PR)
  • Stable disease with hematological improvement (HI)
  • Progression 2

• Achievement of hematological improvement (HI) should be considered indicative of response, as it has been associated with prolongation of survival 2

Important Clinical Considerations

• At least 6 courses of azacitidine are recommended before evaluating efficacy, as many patients respond only after several courses 2

• AML-like intensive chemotherapy has limited indications in higher-risk MDS patients 2

• Azacitidine before HSCT appears promising and is currently being evaluated in clinical trials 2

• The use of HMAs in lower-risk MDS patients who fail other therapies or have multiple cytopenias should be considered 4

• Regular follow-up with complete blood counts and assessment of stability of blood counts over time is essential, with repeat bone marrow examinations as clinically indicated 1