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

Treatment of Myelodysplastic Syndrome (MDS)

Treatment for MDS should be risk-stratified based on the patient's IPSS-R classification, with allogeneic stem cell transplantation being the only potentially curative option for eligible patients. 1

Risk Stratification

MDS treatment approaches are determined primarily by risk category:

1. Lower-risk MDS (IPSS low and INT-1 categories, or WPSS very low, low, and intermediate categories)

   • Primary goal: Hematologic improvement
   • Median survival: 3-10 years

2. Higher-risk MDS (IPSS INT-2 and high categories, or WPSS high and very high categories)

   • Primary goal: Alteration of disease natural history
   • Median survival: Less than 3 years

Treatment Options

Supportive Care (All Patients)

• RBC transfusions for symptomatic anemia (generally leukocyte-reduced)
• Platelet transfusions for severe thrombocytopenia or bleeding
• Antibiotics for infections
• Psychosocial support and quality-of-life assessment
• Iron chelation therapy for heavily transfused patients 2, 1

Lower-Risk MDS Treatment

1. Erythropoiesis-Stimulating Agents (ESAs) ± G-CSF

   • Indication: Serum erythropoietin <500 U/L
   • Response rate: 40-60%
   • Can improve anemia in 15-40% of patients for 8-23 months 1, 3

2. Lenalidomide

   • Indication: MDS with del(5q)
   • Response rate: 60-65%
   • Can lead to complete erythroid response and cytogenetic remission 1, 4

3. Luspatercept

   • Indication: MDS with ring sideroblasts (MDS-RS) or SF3B1 mutation 1

4. Immunosuppressive Therapy

   • Anti-thymocyte globulin (ATG) ± cyclosporine
   • Indication: Failed ESA treatment, younger patients (<65 years)
   • Response rate: 25-40% 1, 4

5. Hypomethylating Agents (HMAs)

   • Indication: Failed ESA treatment
   • Response rate: 30-40% 1

Higher-Risk MDS Treatment

1. Hypomethylating Agents

   • Azacitidine or decitabine
   • Standard of care for patients not eligible for transplantation
   • Prolongs survival and time to leukemic transformation 5, 6
   • Decitabine dosing options:
     • Three-day regimen: 15 mg/m² IV over 3 hours every 8 hours for 3 days, repeated every 6 weeks
     • Five-day regimen: 20 mg/m² IV over 1 hour daily for 5 days, repeated every 4 weeks 5

2. Allogeneic Stem Cell Transplantation

   • Only potentially curative option
   • Consider for eligible patients ≤70 years with available donor
   • Relapse remains the main cause of transplant failure 1, 6

Special Considerations

• Secondary (therapy-related) MDS: Generally has poorer prognosis; manage as higher-risk disease 2

• Monitoring:

  • Regular complete blood counts
  • Assessment of blood count stability over time
  • Repeat bone marrow examinations as clinically indicated
  • Monitor for disease progression or transformation to AML 1

• Iron overload management:

  • Monitor serum ferritin levels and number of RBC transfusions
  • Goal: Decrease ferritin levels to less than 1000 mcg/L 2

Treatment Algorithm

1. Determine risk category using IPSS-R or WPSS
2. Provide supportive care for all patients
3. For lower-risk MDS:
   • If del(5q): Lenalidomide
   • If anemia with low serum erythropoietin: ESAs ± G-CSF
   • If ring sideroblasts or SF3B1 mutation: Luspatercept
   • If failed ESA: Consider ATG ± cyclosporine (younger patients) or HMAs
4. For higher-risk MDS:
   • If eligible for transplant: Allogeneic stem cell transplantation
   • If not eligible for transplant: Hypomethylating agents (azacitidine or decitabine)

The treatment landscape for MDS has evolved significantly, with several effective options now available beyond supportive care, though outcomes remain suboptimal for many patients, particularly those with higher-risk disease who are not transplant candidates 6, 3.