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Erythropoiesis-Stimulating Agents Recommended for Some Patients With Cancer and Anemia


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ASCO and the American Society of Hematology (ASH) have released an update to existing guidelines for use of erythropoiesis-stimulating agents to manage anemia in patients with cancer.1

“The current update aims to increase awareness of recent developments regarding the use of erythropoiesis-stimulating agents in patients with cancer. New information has emerged that may not be widely disseminated, regarding safety, efficacy, and mode of use. This update aims to improve efficacy and, most importantly, safety of erythropoiesis-stimulating agent use in patients,” said Alejandro Lazo-Langner, MD, MSc, FRCPC, of Western University, in Canada, who serves as Co-Chair of the ASCO/ASH Expert Panel that developed the guideline update.


The use of erythropoiesis-stimulating agents in patients with cancer should be limited to a few clinical scenarios after a careful consideration of benefits and risk.
— Alejandro Lazo-Langner, MD, MSc, FRCPC

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Erythropoiesis-stimulating agents are indicated for use in patients with cancer who receive noncurative myelosuppressive chemotherapy that is intended to mitigate symptoms and side effects to decrease the need for red blood cell transfusions. Although erythropoiesis-stimulating agents raise hemoglobin levels and reduce the need for transfusions, they increase the risk of thromboembolic events such as pulmonary embolism, highlighting the ongoing importance of appropriate and careful use. Clinicians and their patients must weigh the benefits and risks when deciding to use such agents.

“The general indication for erythropoiesis-stimulating agents in cancer is to reduce transfusions because the risks may outweigh the benefits, except for those patients with myelodysplastic syndromes,” Dr. Lazo-Langner said.

Evidence Review

ASCO and ASH first published a joint evidence-based clinical practice guideline for the use of erythropoiesis-stimulating agents in adults with cancer and anemia in 2002, with updates in 2007 and 2010. Since the 2010 update, additional information has emerged about the safety and efficacy of erythropoiesis-stimulating agents in patients with metastatic breast cancer and the role of iron when administered along with erythropoiesis-stimulating agents. Treatment options have also expanded with the 2018 U.S. Food and Drug Administration approval of the biosimilar epoetin alfa, which led to an important guideline update.

To update the guideline, ASCO convened an Expert Panel to review the evidence and revise previous recommendations. The panel conducted an in-depth literature review of randomized controlled trials and meta-analyses of randomized controlled trials in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar erythropoiesis-stimulating agents, the literature search was expanded to include meta-analyses and randomized controlled trials in patients with cancer or chronic kidney disease and cohort studies in patients with cancer, due to limited randomized controlled trial evidence in the cancer setting.

Clinical Questions and Recommendations

The guideline addresses the following 10 clinical questions about erythropoiesis-stimulating agents in its recommendations:

  1. To reduce the need for red blood cell transfusions, should erythropoiesis-stimulating agents be offered to patients who have chemotherapy-associated anemia?
  2. To reduce the need for red blood cell transfusions, should erythropoiesis-stimulating agents be offered to anemic patients who are not receiving concurrent myelosuppressive chemotherapy?
  3. What special considerations apply to adult patients with nonmyeloid hematologic malignancies who are receiving concurrent myelosuppressive chemotherapy?
  4. What examinations and diagnostic tests should be performed to identify patients who are likely to benefit from an erythropoiesis-stimulating agent?
  5. Among adult patients who receive an erythropoiesis-stimulating agent for chemotherapy-associated anemia, do darbepoetin, epoetin beta and alfa originators, and currently available biosimilars of epoetin alfa differ with respect to safety or efficacy?
  6. Do erythropoiesis-stimulating agents increase the risk of thromboembolism?
  7. Among adult patients who will receive an erythropoiesis-stimulating agent for chemotherapy-associated anemia, what are the recommendations for erythropoiesis-stimulating agent dosing and dose modifications?
  8. Among adult patients who will receive an erythropoiesis-stimulating agent for chemotherapy-associated anemia, what is the recommended target hemoglobin (Hb) level?
  9. Among adult patients with chemotherapy-associated anemia who do not respond to erythropoiesis-stimulating agent therapy (< 1–2 g/dL increase in Hb or no decrease in transfusion requirements), does continuation of erythropoiesis-stimulating agent therapy beyond 6 to 8 weeks provide a benefit?
  10. Among adult patients with chemotherapy-associated anemia, does iron supplementation concurrent with an erythropoiesis-stimulating agent reduce transfusion -requirements?

“This guideline may provide the necessary information to promote a more rational use of these agents, considering their potential side effects,” Dr. Lazo-Langner said.

The guideline offers a few recommendations on whether erythropoiesis-stimulating agents should be used to reduce the need for red blood cell transfusions in patients who have chemotherapy-associated anemia. The guideline recommends that erythropoiesis-stimulating agents should be used only in certain clinical circumstances, including in patients whose treatment is not curative in intent and whose Hb has declined to < 10 g/dL. It also suggests that red blood cell transfusion is still an option for these patients, but only depending on the severity of their anemia or, again, the specific clinical situation.

Additionally, the update addresses the risk of thromboembolism from erythropoiesis-stimulating agents. Erythropoiesis-stimulating agents increase the risk of thromboembolism, and the guideline warns clinicians to carefully weigh the risks of thromboembolism and proceed with caution and clinical judgment when considering using erythropoiesis-stimulating agents.

Conclusion

Although the use of erythropoiesis-stimulating agents reduces the need for transfusions in anemic patients with cancer receiving chemotherapy, it is associated with increased complications, including higher mortality and increased risk of thromboembolic and cardiovascular events. For these reasons, the use of erythropoiesis-stimulating agents in cancer is now generally limited to patients who are receiving chemotherapy with palliative intent and who are expected to have short survival. The decision to use erythropoiesis-stimulating agents must be made in this context and with a thorough discussion regarding each patient’s preferences, priorities, values, and spiritual needs.

“The use of erythropoiesis-stimulating agents in patients with cancer should be limited to a few clinical scenarios after a careful consideration of benefits and risks,” Dr. Lazo-Langner said.

The guideline stresses the importance of patient counseling regarding the risks and benefits of erythropoiesis-stimulating agent therapy in the decision-making process. The Expert Panel encourages physicians to have open communication with their patients, considering both the scientific evidence and the patient’s diagnosis. 

DISCLOSURE: For full disclosures of the panel authors, visit www.jco.ascopubs.org.

REFERENCE

1. 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. April 10, 2019 (early release online).

Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, April 10, 2019. All rights reserved.


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