The ASCO/ASH guideline contains recommendations which are updated based on the availability of additional information about the safety and efficacy of ESAs in patients with metastatic breast cancer, the role of iron in conjunction with ESAs and new approved drugs.

Erythropoiesis-stimulating agents (ESA) help manage anaemia and reduce the requirement for RBC transfusions. As per the ASCO/ASH clinical practice guideline, erythropoiesis-stimulating agents may be offered to patients with chemotherapy-associated anaemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to <10 g/dL. RBC transfusion is also an option. With the exception of selected patients with myelodysplastic syndromes, ESAs should not be offered to most patients with nonchemotherapy-associated anaemia.

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ESAs in patients who have chemotherapy-associated anaemia

Recommendation: Depending on clinical circumstances, ESAs may be offered to patients with chemotherapy-associated anaemia whose cancer treatment is not curative in intent and whose haemoglobin (HgB) has declined to <10 g/dL. RBC transfusion is also an option, depending on the severity of the anaemia or clinical circumstances.

Recommendation: ESAs should not be offered to patients with chemotherapy-associated anaemia whose cancer treatment is curative in intent.

The decision to limit the indication for ESAs to patients undergoing chemotherapy for palliation is based on the known risks, such as increased risk for thromboembolic events and short-term mortality and decreased overall survival. The authors add that the goal of treatment would require clinical judgment.

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ESAs in anaemic patients with cancer who are not receiving concurrent myelosuppressive chemotherapy

Recommendation: ESAs should not be offered to most patients with nonchemotherapy-associated anaemia.

Recommendation: ESAs may be offered to patients with lower risk myelodysplastic syndromes and a serum erythropoietin level ≤ 500 IU/L.

The relative effects of ESAs to reduce the risk for RBC transfusions in patients with and without myelosuppressive chemotherapy is not supported by relevant evidence, but, as per the current licensing, ESAs are only indicated in patients who are anaemic from concurrent myelosuppressive chemotherapy and not in patients with cancer who are not receiving concurrent myelosuppressive chemotherapy.

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Special considerations in adult patients with nonmyeloid hematologic malignancies who are receiving concurrent myelosuppressive chemotherapy

Recommendation: 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. In all cases, blood transfusion is a treatment option that should be considered.

As the above mentioned malignancies recur in most patients and a multitude of treatments are currently available, determining the treatment intent and the expected survival should involve clinical judgment of an individual patient’s circumstances. In addition to this, the risks of complications such as thromboembolic events (for example with immunomodulatory drugs in multiple myeloma) must be taken into account.

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Examinations and diagnostic tests required before making a decision about using an ESA to identify patients who are likely to benefit from an ESA

Recommendation: Before offering an ESA, clinicians should conduct an appropriate history, physical examination, and diagnostic tests to identify alternative causes of anaemia aside from chemotherapy or an underlying hematopoietic malignancy. Such causes should be appropriately addressed before considering the use of ESAs.

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Among adult patients who receive an ESA for chemotherapy-associated anaemia, do darbepoetin, epoetin beta and alfa originator, and currently available biosimilars of epoetin alfa differ with respect to safety or efficacy

Recommendation: The Expert Panel considers epoetin beta and alfa, darbepoetin, and biosimilar epoetin alfa to be equivalent with respect to effectiveness and safety.

The panel suggests that addressing reversible causes of anaemia should be the preferred initial approach as the use of ESAs is associated with risks, especially thrombotic risk.

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ESAs and the risk of thromboembolism

Recommendation: 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.

Patients receiving ESA therapy have a 50% to 75% increased risk of thromboembolism and vascular arterial events, hence, caution should be exercised in patients at an increased risk for venous thromboembolism. Multiple myeloma patients being treated with thalidomide or lenalidomide and doxorubicin or corticosteroids are at particularly increased thrombotic risk; hence special attention is warranted in this group of patients.

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ESA dosing and dose modifications in adult patients who will receive an ESA for chemotherapy-associated anaemia

Recommendation: It is recommended that starting and modifying doses of ESAs follow FDA guidelines.

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Recommended target HgB level in adult patients who will receive an ESA for chemotherapy-associated anaemia

Recommendation: 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.

The panel suggests that modifications to reduce the ESA dose are appropriate when HgB reaches a level sufficient to avoid transfusion or the increase exceeds 1 g/dL in any 2-week period to avoid excessive ESA exposure. These suggestions have been made due to the risks associated with ESA.

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Among adult patients with chemotherapy-associated anaemia who do not respond to ESA therapy (<1 to 2 g/dL increase in HgB or no decrease in transfusion requirements), does continuation of ESA therapy beyond 6 to 8 weeks provide a benefit?

Recommendation: ESAs should be discontinued in patients who do not respond within 6 to 8 weeks. Patients who do not respond to ESA treatment should be reevaluated for underlying tumor progression, iron deficiency, or other etiologies for anaemia.

The panel suggests cessation of ESA in patients who do not respond even after receiving appropriate dosing. In this manner, the exposure to ESAs can be minimised.

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The role of iron supplementation concurrent with an ESA in reducing transfusion requirements in adult patients with chemotherapy-associated anaemia

Recommendation: 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 ferritin levels is recommended.

Evidence shows that iron supplementation reduces the risk for RBC transfusion. In patients with evidence of iron deficiency, the panel suggests to investigate and correct the cause of the deficiency.

Though both oral and IV iron formulations are acceptable options, in IV iron preparations larger amounts of elemental iron can be delivered in a single application. Additionally, IV preparations may be suitable in patients with poor oral intake or absorption problems. IV iron preparations are however, associated with serious systemic reactions.

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Reference: Bohlius J, Bohlke K, Castelli R, et al. Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update. J Clin Oncol. 2019;37(15):1336-1351. doi: 10.1200/JCO.18.02142.