SUMMARY: The American Society of Clinical Oncology (ASCO) along with American Society of Hematology (ASH) updated recommendations for use of Erythropoiesis Stimulating Agents (ESAs) in patients with cancer. The primary literature review included 15 meta-analyses of Randomized Clinical Trials and two Randomized Clinical Trials. These recommendations were developed using a systematic review of the literature from January, 2010, through May, 2018, and clinical experience.
Guideline question: When and how should Erythropoiesis Stimulating Agents (ESAs) be used to manage anemia in adults with cancer?
Target population: Adults with Cancer and Anemia.
Target audience: Oncologists, Hematologists, Oncology Nurses, Oncology Pharmacists, and other health care professionals who care for patients with cancer, and patients with cancer.
Clinical question 1: To reduce the need for RBC transfusions, should ESAs be offered to patients who have chemotherapy-associated anemia?
Recommendation 1.1. Depending on clinical circumstances, ESAs may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to less than 10 g/dL. RBC transfusion is also an option, depending on the severity of the anemia or clinical circumstances
Recommendation 1.2. ESAs should not be offered to patients with chemotherapy-associated anemia whose cancer treatment is curative in intent
Clinical question 2: To reduce the need for RBC transfusions, should ESAs be offered to anemic patients with cancer who are not receiving concurrent myelosuppressive chemotherapy?
Recommendation 2.1. ESAs should not be offered to most patients with nonchemotherapy-associated anemia
Recommendation 2.2. ESAs may be offered to patients with lower risk MyeloDysplastic Syndromes and a serum Erythropoietin level 500 IU/L or less.
Clinical question 3: What special considerations apply to adult patients with nonmyeloid hematologic malignancies who are receiving concurrent myelosuppressive chemotherapy?
Recommendation 3. In patients with Myeloma, Non-Hodgkin Lymphoma, or Chronic Lymphocytic Leukemia, clinicians should observe the hematologic response to cancer treatment before considering an ESA. Particular caution should be exercised in the use of ESAs concomitant with treatment strategies and diseases where risk of thromboembolic complications is increased (see Recommendations 4 and 6). In all cases, blood transfusion is a treatment option that should be considered
Clinical question 4: What examinations and diagnostic tests should be performed before making a decision about using an ESA to identify patients who are likely to benefit from an ESA?
Recommendation 4. Before offering an ESA, clinicians should conduct an appropriate history, physical examination, and diagnostic tests to identify alternative causes of anemia aside from chemotherapy or an underlying hematopoietic malignancy. Such causes should be appropriately addressed before considering the use of ESAs. Suggested baseline investigations include thorough drug exposure history, peripheral blood smear review, analyses where indicated, for Iron, TIBC, Ferritin, Transferrin saturation, Folate, Vitamin B12, or Hemoglobinopathy screening, assessment of Reticulocyte count, occult blood loss and renal Insufficiency and baseline Erythropoietin level and TSH. Investigations may also include Direct Antiglobulin Testing (eg, Coombs test) for patients with Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or a history of autoimmune disease.
Clinical question 5: Among adult patients who receive an ESA for chemotherapy-associated anemia, do Darbepoetin, Epoetin beta and alfa originator, and currently available biosimilars of Epoetin alfa differ with respect to safety or efficacy?
Recommendation 5. The Expert Panel considers Epoetin beta and alfa, Darbepoetin, and biosimilar Epoetin alfa to be equivalent with respect to effectiveness and safety
Clinical question 6: Do ESAs increase the risk of thromboembolism?
Recommendation 6. ESAs increase the risk of thromboembolism, and clinicians should carefully weigh the risks of thromboembolism and use caution and clinical judgment when considering use of these agents
Clinical question 7: Among adult patients who will receive an ESA for chemotherapy-associated anemia, what are recommendations for ESA dosing and dose modifications?
Recommendation 7. It is recommended that starting and modifying doses of ESAs follow FDA guidelines
Clinical question 8: Among adult patients who will receive an ESA for chemotherapy-associated anemia, what is the recommended target HgB level?
Recommendation 8. HgB may be increased to the lowest concentration needed to avoid or reduce the need for RBC transfusions, which may vary by patient and condition
Clinical question 9: Among adult patients with chemotherapy-associated anemia who do not respond to ESA therapy (less than 1 to 2 g/dL increase in HgB or no decrease in transfusion requirements), does continuation of ESA therapy beyond 6-8 weeks provide a benefit?
Recommendation 9. ESAs should be discontinued in patients who do not respond within 6-8 weeks. Patients who do not respond to ESA treatment should be reevaluated for underlying tumor progression, Iron deficiency, or other etiologies for anemia
Clinical question 10: Among adult patients with chemotherapy-associated anemia, does Iron supplementation concurrent with an ESA reduce transfusion requirements?
Recommendation 10. Iron replacement may be used to improve HgB response and reduce RBC transfusions for patients receiving ESA with or without iron deficiency. Baseline and periodic monitoring of Iron, total Iron-Binding Capacity, Transferrin saturation, or Frritin levels is recommended
Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update. Bohlius J, Bohlke K, Castelli R, et al. Blood Advances 2019;3:1197-1210