Manage Cancer-Associated Anemia With Erythropoietin-Stimulating Agents

Transfusions and ESAs

Management of symptomatic, cancer-associated anemia typically includes transfusion of packed red blood cells (RBCs) and use of erythropoietin-stimulating agents (ESAs). Blood transfusions may correct anemia when a quicker result is desired because of symptoms or comorbidities. Transfusions have associated risks (https://www.uptodate.com/contents/practical-aspects-of-red-blood-cell-transfusion-in-adults-storage-processing-modifications-and-infusion), including acute reactions, volume overload, contamination or other infectious risk, and other long-term side effects such as iron overload, which need to be considered.

Synthetic erythropoietin, such as epoetin alfa and darbepoetin alfa, is commonly used to raise hemoglobin levels and reduce the need for RBC transfusions for certain patients with cancer-associated anemia. ESAs may be considered especially if a patient declines blood transfusions. Despite ESAs’ effectiveness, multiple meta-analyses have addressed their potential risks (https://doi.org/10.1002/14651858.CD003407.pub5), including thrombosis, cancer progression, recurrence, and decreased survival. Also, ESAs typically take weeks to elicit a response and repeated administration is often required to maintain a target hemoglobin level. Advanced practice providers must understand the risks and benefits when considering ESAs for their patients.

Clinical Practice Guidelines

The American Society of Clinical Oncology/American Society of Hematology clinical practice guidelines for managing cancer-associated anemia (https://doi.org/10.1200/JCO.18.02142) with ESAs were updated in April 2019 by a multidisciplinary expert panel that recommended more restrictions after a review of the prior guidelines and current literature. Clinical questions were addressed, and the panel recommended that:

• Depending on clinical circumstances, ESAs may be offered to select patients receiving noncurative myelosuppressive chemotherapy who have hemoglobin levels less than 10g/dl.
• ESAs maybe considered in patients with lower-risk myelodysplastic syndrome and a serum erythropoietin level of less than 500 IU/l.
• For patients with nonmyeloid hematologic malignancies who are receiving palliative chemotherapy, observe the hematologic response to cancer treatment before considering ESAs.
• Use ESAs with extreme caution or avoid them altogether for patients whose disease or treatments are associated with increased risk of thromboembolic complications (e.g., patients with multiple myeloma receiving immunomodulators such as thalidomide or lenolidomide).
• When ordering ESAs for cancer-associated anemia, starting doses and modifications (which are outlined in a table in the guidelines) should follow U.S. Food and Drug Administration’s (https://www.fda.gov/Drugs/DrugSafety/ucm109375.htm) approved labeling. If hemoglobin does not improve in six to eight weeks, discontinue and rule out other causes.

The panel also recommended that providers consider concurrent iron supplementation in patients receiving ESAs. Chemotherapy is associated with abnormal iron metabolism and studies have shown (https://doi.org/10.1200/JCO.2004.08.119) that supplementation improved ESA efficacy even in the absence of documented iron deficiency.

Advanced practice providers should incorporate proper differential diagnosis and identify and manage alternate causes of anemia. Ongoing patient education and counseling regarding the risks and benefits of blood transfusions and ESAs will help to ensure that patients are making informed decisions.

ESAs can be effective in reducing the need for blood transfusions and improving symptoms but must be used in a safe manner. By keeping up to date with the most recent literature and practice guidelines, advanced practice providers will be able to effectively and safely manage their patients with common toxicities such as anemia.