What is the treatment for Myelodysplastic Syndrome (MDS)?

Treatment of Myelodysplastic Syndrome (MDS)

Treatment for MDS should be risk-stratified based on prognostic scoring systems, with different approaches for lower-risk versus higher-risk disease to optimize survival and quality of life. 1

Risk Stratification

Before initiating treatment, patients should be stratified into risk categories using validated prognostic scoring systems:

• Lower-risk MDS: IPSS low/int-1, IPSS-R very low/low/intermediate, WPSS very low/low/intermediate
• Higher-risk MDS: IPSS int-2/high, IPSS-R intermediate/high/very high, WPSS high/very high

Note: Patients with IPSS-R intermediate may be managed as either lower or higher risk depending on additional factors like age, performance status, serum ferritin and LDH levels. 1

Treatment Algorithm

1. Supportive Care (All Patients)

All MDS patients require supportive care, which includes:

• RBC transfusions for symptomatic anemia (maintain hemoglobin ≥8 g/dL, or ≥9-10 g/dL in patients with comorbidities or poor tolerance) 1
• Platelet transfusions for severe thrombocytopenia or bleeding
• Antibiotics for neutropenic infections (not prophylactically)
• Iron chelation therapy for patients with transfusional iron overload (serum ferritin >1000 mcg/L after receiving 20-60 RBC units) 1
• Psychosocial support and patient support group referrals 1

2. Lower-Risk MDS Treatment

For Anemia:

1. Erythropoiesis-stimulating agents (ESAs) - first-line therapy

   • Recombinant human erythropoietin or darbepoetin
   • Better response in patients with low baseline serum erythropoietin levels (<500 mU/mL) and low transfusion requirements (<2 units/month) 1
   • May be combined with G-CSF for synergistic effect

2. Lenalidomide - for patients with del(5q)

   • FDA-approved for transfusion-dependent anemia in lower-risk MDS with del(5q) 2
   • Achieves transfusion independence in 67% of del(5q) patients
   • Also effective in 25-30% of non-del(5q) patients after ESA failure 1

3. Immunosuppressive therapy (anti-thymocyte globulin ± cyclosporine)

   • Consider for younger patients (<65 years) with hypocellular marrow, HLA-DR15 genotype, short transfusion history, normal karyotype or trisomy 8 1

4. Hypomethylating agents (azacitidine, decitabine)

   • Can achieve RBC transfusion independence in 30-40% of lower-risk patients 1
   • FDA-approved for all MDS subtypes 3

For Thrombocytopenia:

• High-dose androgens - can improve thrombocytopenia in about one-third of patients, but responses are typically transient 1
• Thrombopoietin receptor agonists (romiplostim, eltrombopag) - under investigation, showing promising results 1
• Immunosuppressive therapy or hypomethylating agents - may improve platelet counts in 35-40% of cases 1

For Neutropenia:

• G-CSF for neutropenic fever or severe infections, not for routine prophylaxis 1

3. Higher-Risk MDS Treatment

1. Hypomethylating agents - first-line therapy for most patients

   • Azacitidine or decitabine
   • Prolongs time to leukemic transformation and improves survival 1, 3
   • Administer for at least 6 cycles before assessing response 1

2. Allogeneic hematopoietic stem cell transplantation (HSCT)

   • Only potentially curative option 4, 5
   • Consider for eligible patients <65-70 years with good performance status
   • Should be considered early in the disease course 1

3. AML-like chemotherapy

   • Alternative for fit patients without access to hypomethylating agents or clinical trials
   • Higher response rates but similar survival to hypomethylating agents 1

4. Clinical trials - consider for patients who fail first-line therapy

Special Considerations

• Therapy-related MDS: Generally managed as higher-risk disease due to poor prognosis 1
• Iron overload management: Consider chelation therapy for patients with serum ferritin >1000 mcg/L who have received multiple transfusions, especially transplant candidates 1
• Elderly or frail patients: May benefit from dose-adjusted regimens or supportive care only 1

Treatment Response Assessment

• Monitor complete blood counts regularly (weekly for first 8 weeks of therapy for del(5q) MDS, then monthly) 2
• Evaluate bone marrow periodically to assess disease status and response
• Use standardized International Working Group response criteria to assess outcomes 1

Common Pitfalls to Avoid

• Delayed recognition of disease progression: Regular monitoring is essential
• Inadequate iron chelation: Can lead to organ damage in transfusion-dependent patients
• Premature discontinuation of therapy: Hypomethylating agents may require 4-6 cycles before response is observed
• Overlooking transplant eligibility: Early HLA typing and donor search should be initiated for eligible higher-risk patients
• Undertreatment of anemia: Maintaining adequate hemoglobin levels improves quality of life

Remember that while supportive care is essential for all patients, disease-modifying therapy should be considered based on risk stratification to improve survival and quality of life.