An expert panel recently convened to update clinical practice guideline recommendations for the management of cancer-associated anemia with erythropoiesis-stimulating agents (ESAs) based on a systematic review of the medical literature.

The American Society of Clinical Oncology (ASCO) and the American Society of Hematology (ASH) first published the evidence-based clinical practice guideline in 2002. The update, which was published in Blood Advances1 and the Journal of Clinical Oncology2, comes nearly 10 years after the last update in 2010.

“In summary, the guideline update says that we can use ESAs in patients with cancer who are on palliative treatment and in those patients with anemia in whom you want to decrease transfusion use. That was a confirmation of the previous guideline, but there is more evidence supporting this view given the risk associated with the use of ESAs in this setting. The only exception to that is the use of ESAs in myelodysplastic syndromes,” said Alejandro Lazo-Langner, MD, of Western University in Canada, who was the expert panel cochair and senior author of the guideline update.

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“These guidelines do include biosimilars, which were not included in the previous version,” explained Dr Lazo-Langner. “And there is now a stronger recommendation regarding the concurrent use of iron supplementation to improve the efficacy of ESA treatment.”

The multidisciplinary expert panel included 13 members, including a patient representative and an ASCO guidelines staff member with health research methodology expertise. After the panel developed the recommendations, public comments on the recommendations from a 2-week open comment period were also taken into account. Additionally, the ASCO Clinical Practice Guidelines Committee, the ASH Guideline Oversight Subcommittee, the ASH Committee on Quality, and ASH Officers reviewed and approved the recommendations.

To update the guidelines, the panel addressed 10 clinical questions surrounding ESA use for treatment of cancer-associated anemia by conducting a systematic literature review from January 31, 2010, to May 14, 2018, and by drawing upon clinical experience (Table). PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs on the safety and efficacy of ESAs in patients with cancer. For the question on biosimilars, the search also included RCTs and meta-analyses of RCTs including patients with cancer or chronic kidney disease (CKD) or cohort studies in patients with cancer.

Table. Clinical Questions for the Use of ESAs for Treatment of Cancer-Associated Anemia
1. To reduce the need for red blood cell (RBC) transfusions, should ESAs be offered to patients who have chemotherapy-associated anemia?
2. To reduce the need for RBC transfusions, should ESAs be offered to anemic patients with cancer 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 before making a decision about using an ESA to identify patients who are likely to benefit from an ESA?
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?
6. Do ESAs increase the risk for thromboembolism?
7. Among adult patients who will receive an ESA for chemotherapy-associated anemia, what are recommendations for ESA dosing and dose modifications?
8. Among adult patients who will receive an ESA for chemotherapy-associated anemia, what is the recommended target hemoglobin (HgB) level?
9. Among adult patients with chemotherapy-associated anemia who do not respond to ESA therapy (less than 1-2 g/dL increase in HgB or no decrease in transfusion requirements), does continuation of ESA therapy beyond 6 to 8 weeks provide a benefit?
10. Among adult patients with chemotherapy-associated anemia, does iron supplementation concurrent with an ESA reduce transfusion requirements?