Can Erythropoiesis-Stimulating Agents (ESAs) be used in patients with multiple myeloma undergoing dialysis due to impaired renal function?

ESA Use in Multiple Myeloma Dialysis Patients

Yes, ESAs can be used in multiple myeloma patients on dialysis, but only when hemoglobin is <10 g/dL with persistent symptomatic anemia after excluding reversible causes, and with heightened awareness of thromboembolic risk that is particularly elevated in this population. 1

When to Initiate ESA Therapy

• Start ESAs only when hemoglobin falls below 10 g/dL with documented symptomatic anemia, not prophylactically. 1, 2

• Before initiating any ESA, you must exclude and correct:

  • Iron deficiency (check ferritin and transferrin saturation) 1, 3
  • Vitamin B12 deficiency 1
  • Hemolysis 1
  • Functional iron deficiency, which is common and causes ESA hyporesponsiveness 2, 4

• The European Myeloma Network emphasizes that with modern effective combination therapies that rapidly control myeloma, the systematic need for ESAs is debatable. 1

Standard Dosing Regimens

For dialysis patients with multiple myeloma, use these specific doses: 1, 2

• Epoetin alfa: 40,000 U subcutaneously weekly
• Epoetin beta: 30,000 U subcutaneously weekly
• Darbepoetin: 150 μg weekly OR 500 μg every 3 weeks

Critical Safety Considerations for This Population

The thromboembolic risk is markedly elevated in multiple myeloma patients, especially those receiving thalidomide or lenalidomide with dexamethasone or doxorubicin. 1, 2

• ESAs increase the relative risk of thromboembolic events by 67% compared to placebo (RR 1.67; 95% CI: 1.35-2.06). 1

• Implement thromboprophylaxis concurrently: 1, 2

  • For 0-1 individual risk factors: aspirin 100 mg daily
  • For ≥2 risk factors or high-dose dexamethasone/multiagent chemotherapy: LMWH or full-dose warfarin

• Recent data from Denmark showed MM patients on ESAs had adjusted HR of 1.41 for VTE, 1.23 for MI, and 1.63 for stroke, though confidence intervals included equivalence. 5

Hemoglobin Targets and Monitoring

Target hemoglobin range is 10-12 g/dL; never exceed 12 g/dL. 1, 2, 3

• Exceeding 12 g/dL increases cardiovascular and thromboembolic risks as well as possibly mortality. 1

• Discontinue ESAs after 6-8 weeks if adequate hemoglobin response is not achieved (defined as <1 g/dL increase at 4-6 weeks). 1, 2

Mandatory Iron Supplementation Strategy

Most patients require concurrent intravenous iron to optimize ESA response and minimize required ESA doses. 1, 2, 3

• For dialysis patients, administer IV iron if ferritin <200 ng/mL and transferrin saturation <20%. 3

• Standard dosing is IV iron sucrose 1000 mg total dose. 3

• Functional iron deficiency during ESA treatment should be treated with IV iron (grade 1A recommendation). 1

Common Pitfalls to Avoid

• Never initiate ESAs at hemoglobin ≥10 g/dL unless there are compelling clinical circumstances. 2

• Do not continue ESAs beyond 6-8 weeks in non-responders. 1, 2

• Do not use ESAs in patients with poorly controlled hypertension. 1

• The thrombotic risk is not a contraindication to IV iron itself, only to ESAs. 3