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

Treatment Options for Myelodysplastic Syndrome (MDS) Anemia

Erythropoiesis-stimulating agents (ESAs) are the first-line treatment for anemia in most lower-risk MDS without del(5q), with weekly doses of 30,000-80,000 units of erythropoietin or 150-300 μg of darbepoetin yielding 40-60% response rates when baseline serum erythropoietin levels are low (<500 mU/mL) and transfusion requirements are limited. 1

First-Line Treatment Approach

For Lower-Risk MDS without del(5q):

• ESAs (erythropoietin or darbepoetin) 1

  • Dosing:
    • Erythropoietin: 30,000-80,000 units weekly subcutaneously
    • Darbepoetin: 150-300 μg weekly subcutaneously
  • Response evaluation: Within 6-8 weeks of treatment
  • Response duration: Median 20-24 months
  • Predictors of response:
    • Low baseline serum erythropoietin (<200-500 mU/mL)
    • Limited or no RBC transfusion requirements
    • Marrow blasts <5%
    • No multi-lineage dysplasia

• ESAs + G-CSF combination for enhanced response 1

  • G-CSF dosing: 1-2 μg/kg daily or 1-3 times weekly
  • Particularly effective in patients with ≥15% ringed sideroblasts
  • Synergistic effect improves erythroid response rates

For Lower-Risk MDS with del(5q):

• Lenalidomide 1
  • Dosing: 10 mg/day for 3 weeks every 4 weeks
  • Response rate: 60-65% achieve transfusion independence
  • Duration of response: 2-2.5 years median
  • Cytogenetic response in 50-75% of patients
  • Monitor for neutropenia and thrombocytopenia (common adverse effects)

Second-Line Treatment Options

For ESA Failure in Non-del(5q) MDS:

1. Immunosuppressive therapy 1

   • Anti-thymocyte globulin (ATG) ± cyclosporine
   • Response rate: 25-40%
   • Best results in younger patients (<65 years), short transfusion history (<2 years), normal karyotype, HLA-DR15 genotype

2. Hypomethylating agents (HMAs) 1

   • Response rate: 30-40% achieve transfusion independence
   • Also effective for other cytopenias

3. Lenalidomide 1

   • Response rate: 25-30% in non-del(5q) MDS
   • Combination with ESAs may improve response rates

For Lenalidomide Failure in del(5q) MDS:

• Consider hypomethylating agents or allogeneic stem cell transplantation, particularly in patients with TP53 mutations 1

Supportive Care

• Red blood cell transfusions for symptomatic anemia 1
  • Consider when other treatments fail
  • Monitor for and manage iron overload with chelation therapy in transfusion-dependent patients

Treatment Algorithm

1. Risk stratification: Determine if patient has lower-risk MDS (IPSS low/int-1 or IPSS-R very low/low/intermediate)
2. Cytogenetic assessment: Check for del(5q)
3. For non-del(5q) MDS:
   • Measure serum erythropoietin level
   • If <500 mU/mL: Start ESA therapy
   • If inadequate response after 6-8 weeks: Add G-CSF
   • If no response after combined therapy: Move to second-line options
4. For del(5q) MDS:
   • Start lenalidomide
   • Monitor for cytopenia
   • Consider TP53 mutation testing (associated with poor outcomes)

Important Considerations

• Verify iron repletion before starting ESA therapy 1
• Monitor hemoglobin levels regularly during treatment
• Avoid targeting hemoglobin >12 g/dL due to increased risks of thromboembolic events 1
• ESAs have shown no negative impact on AML progression and may be an independent favorable prognostic factor for survival 1
• Response to ESAs typically occurs within 6-8 weeks; if no response by 8 weeks, consider treatment failure and alternative options 1

By following this structured approach to treating MDS-related anemia, clinicians can improve patients' quality of life, reduce transfusion dependency, and potentially impact overall survival outcomes.