What are the primary indications for erythropoietin-stimulating agents (ESAs)?

Primary Indications for Erythropoietin-Stimulating Agents (ESAs)

The primary indications for erythropoietin-stimulating agents (ESAs) are treatment of anemia due to chronic kidney disease (CKD) in patients on dialysis and not on dialysis, chemotherapy-induced anemia in non-myeloid malignancies when chemotherapy is expected to continue for at least 2 additional months, anemia due to zidovudine in HIV patients, and reduction of allogeneic red blood cell transfusions in patients undergoing elective, noncardiac, nonvascular surgery. 1

Chronic Kidney Disease (CKD)

ESAs are indicated for treating anemia in CKD patients when:

• Hemoglobin levels are sustained below 10 g/dL
• Iron stores have been corrected
• Other reversible causes of anemia have been treated 2

Treatment algorithm for CKD patients:

1. Confirm hemoglobin level is below 10 g/dL
2. Evaluate and correct iron status
3. Rule out other causes of anemia
4. Target hemoglobin level of 11 g/dL (acceptable range: 10-12 g/dL) 2
5. Monitor for hypertension, which must be controlled prior to and during ESA therapy

Cancer-Related Anemia

ESAs are indicated for:

• Patients with non-myeloid malignancies receiving myelosuppressive chemotherapy
• When chemotherapy is expected to continue for at least 2 additional months
• When hemoglobin is less than 10 g/dL 2

Important restrictions:

• ESAs are NOT indicated for cancer patients receiving hormonal agents, biologic products, or radiotherapy unless also receiving concomitant myelosuppressive chemotherapy
• ESAs are NOT indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure
• ESAs are NOT indicated when anemia can be managed by transfusion 1, 3

Treatment algorithm for cancer patients:

1. Confirm hemoglobin level is ≤10 g/dL
2. Verify patient is receiving myelosuppressive chemotherapy with at least 2 months remaining
3. Ensure treatment goal is not curative
4. Target hemoglobin to <12 g/dL
5. Discontinue ESA 4 weeks after completing chemotherapy 2

Other Approved Indications

1. HIV patients on zidovudine: ESAs are indicated for anemia due to zidovudine treatment in HIV-infected patients 1

2. Surgical patients: ESAs are indicated for reduction of allogeneic red blood cell transfusions in patients undergoing elective, noncardiac, nonvascular surgery 1, 2

   • Not indicated for patients willing to donate autologous blood
   • Not indicated for cardiac or vascular surgery
   • Deep vein thrombosis prophylaxis is recommended

Myelodysplastic Syndromes (MDS)

ESAs may be offered to patients with lower-risk MDS and serum erythropoietin level ≤500 IU/L 2

Important Safety Considerations

• Mortality risk: ESAs increase the risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access when targeting hemoglobin levels >11 g/dL 1, 3

• Cancer progression: ESAs can increase the risk of tumor progression or recurrence in certain cancers (breast, non-small cell lung, head and neck, lymphoid, and cervical cancers) 2

• Dosing caution: Use the lowest effective dose to reduce need for transfusions

• Monitoring requirements:

  • Reduce dose if hemoglobin rises >2 g/dL in 4 weeks
  • Withhold dose if hemoglobin exceeds 12 g/dL
  • Monitor blood pressure closely

Contraindications

• Uncontrolled hypertension
• Pure red cell aplasia following previous ESA therapy
• Serious allergic reactions to ESAs 1, 3

ESAs have revolutionized the management of anemia in specific clinical scenarios, but their use must be carefully balanced against potential risks, particularly in cancer patients where survival outcomes may be negatively impacted.