What are the treatment options for Myelodysplastic Syndromes (MDS)?

Treatment Options for Myelodysplastic Syndromes (MDS)

Treatment for Myelodysplastic Syndromes should be risk-stratified based on the International Prognostic Scoring System (IPSS) or revised IPSS (IPSS-R), dividing patients into lower-risk (very low, low, intermediate-1) and higher-risk (intermediate-2, high) categories. 1

Risk Stratification and Initial Evaluation

Initial evaluation should include:

• Complete blood count with reticulocyte count
• Peripheral blood smear
• Bone marrow aspiration and biopsy
• Cytogenetic analysis
• Serum erythropoietin level
• Molecular evaluation (especially for TP53 and SF3B1 mutations)

Treatment for Lower-Risk MDS

Management of Anemia

1. For patients with serum erythropoietin <500 U/L:

   • First-line: Erythropoiesis-stimulating agents (ESAs) ± G-CSF 2, 1
   • Response rate: 40-60%
   • Responses typically occur within 8-12 weeks of treatment 2

2. For patients with serum erythropoietin >500 U/L or requiring ≥2 RBC transfusions/month:

   • For patients with del(5q): Lenalidomide 10 mg/day for 3 weeks every 4 weeks 2

     • Response rate: 60-65% achieve transfusion independence
     • Median duration of response: 2-2.5 years
     • Monitor for neutropenia and thrombocytopenia (occurs in ~60% of patients)

   • For patients with ring sideroblasts (MDS-RS) or SF3B1 mutation: Luspatercept 2, 1

3. Red blood cell transfusions for symptomatic anemia

   • Use leukocyte-reduced products
   • One unit typically increases hemoglobin by ~1 g/dL

Management of Thrombocytopenia

• Platelet transfusions for severe thrombocytopenia or bleeding
• Consider thrombopoietin receptor agonists (romiplostim, eltrombopag) in clinical trials 1

Management of Neutropenia

• Broad-spectrum antibiotics for fever or infection
• Short-term G-CSF during severe infections
• Prophylactic antibiotics or G-CSF are not recommended for routine use 2, 1

Treatment for Higher-Risk MDS

1. For eligible patients ≤70 years:

   • Allogeneic hematopoietic stem cell transplantation (allo-HSCT) - only potentially curative option 1, 3

2. For patients >70 years or not eligible for transplantation:

   • Hypomethylating agents:
     • Azacitidine: 75 mg/m²/day subcutaneously for 7 days every 28 days, minimum 6 cycles 1
     • Decitabine: Either 15 mg/m² by continuous IV infusion over 3 hours every 8 hours for 3 days (repeat cycle every 6 weeks) OR 20 mg/m² by continuous IV infusion over 1 hour daily for 5 days (repeat cycle every 4 weeks) 4

Supportive Care

1. Iron overload management:

   • Monitor iron status in transfusion-dependent patients
   • Consider iron chelation therapy for patients with heavy transfusion requirements at risk for end-organ complications 2, 1
   • Particularly important for future candidates for allogeneic stem cell transplantation 2

2. Psychosocial support:

   • Offer contacts with patient support groups 2, 1

Special Considerations

• TP53 mutations in lower-risk MDS with del(5q) confer resistance to lenalidomide and higher risk of AML progression, requiring intensified disease surveillance 2

• IPSS-R intermediate-risk MDS patients: Treatment approach (whether as lower-risk or higher-risk) should be based on additional factors including age, comorbidities, severity of cytopenias, somatic mutations, and effect of first-line treatment 2

Treatment Algorithm

1. Determine risk category using IPSS or IPSS-R

2. For lower-risk MDS:

   • If symptomatic anemia with serum EPO <500 U/L: ESAs ± G-CSF
   • If del(5q): Lenalidomide
   • If MDS-RS or SF3B1 mutation: Luspatercept
   • If symptomatic thrombocytopenia: Consider TPO receptor agonists
   • If symptomatic neutropenia with fever: Broad-spectrum antibiotics

3. For higher-risk MDS:

   • If eligible: Consider allogeneic stem cell transplantation
   • If ineligible for transplant: Hypomethylating agents (azacitidine or decitabine)

Treatment Response Monitoring

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.