RXMP-31 Erythropoietic Stimulating Agents for Cancer Conditions Form

Erythropoietic Stimulating Agents for Cancer Conditions

Updated on: 12/23/2025

Page 1 of 9 Criteria Short Cuts: Medical Necessity Anemia Due to Cancer Chemotherapy Anemia Associated with Myelodysplastic Syndromes (MDS) Anemia Associated with Myeloproliferative Neoplasms - Myelofibrosis

Policy Number RXMP-31 Line of Business Medicaid & Medicare Effective Date Medicaid 12/1/2025; Medicare: 1/1/2026 Revision Date 12/23/2025

Products: Aranesp (darbepoetin alfa), Epogen (epoetin alfa), Procrit (epoetin alfa), Retacrit (epoetin alfa-epbx)

Override(s)
Approval Duration
Prior Authorization
Initial or renewal: 12 months Preoperative use for reduction of allogeneic blood transfusion in Members undergoing surgery: 3 months

HCPCS Description Medical Benefit: Authorization Required; Pharmacy Benefit: PA required J0881 Injection, darbepoetin alfa, 1 mcg (non-ESRD use) [Aranesp] (preferred) J0882 Injection, darbepoetin alfa, 1 mcg (for ESRD on dialysis) [Aranesp] (preferred) J0885 Injection, epoetin alfa, (for non-ESRD use), 1000 units [Procrit, Epogen] Q4081 Injection, epoetin alfa, 100 units (for ESRD on dialysis) [Procrit, Epogen] Q5105 Injection, epoetin alfa-epbx, biosimilar, (Retacrit) (for ESRD on dialysis), 100 units (preferred) Q5106 Injection, epoetin alfa-epbx, biosimilar, (Retacrit) (for non-ESRD use), 1000 units (preferred) J0887 Injection, epoetin beta, 1 microgram, (for ESRD on dialysis) [Mircera] J0888 Injection, epoetin beta, 1 microgram, (for non-ESRD use) [Mircera]

Medicare Criteria
Medicare Part B Coverage Criteria
Medicare covers Erythropoiesis Stimulating Agents (ESAs) for the treatment of anemia in patients with chronic renal failure who are on dialysis. Refer to the Medicare Benefit Policy Manual, Chapter 15, § 50.5.2- Erythropoietin (EPO).

Erythropoiesis stimulating agents (ESAs) also may be covered for patients with specific clinical indications and who meet coverage criteria. Refer to the National Coverage Determination (NCD) for Erythropoiesis Stimulating Agents (ESAs) in Cancer and Related Neoplastic Conditions (110.21). Local Coverage Determinations (LCDs)/Local Coverage Articles (LCAs) exist; refer to the LCDs/LCAs for LCD - Erythropoiesis Stimulating Agents (ESAs) (L34633) (Accessed as of 11/25/2025).

In general, Medicare covers outpatient (Part B) drugs that are furnished "incident to" a physician's service provided that the drugs are not usually self-administered by the patients who take them. Refer to the Medicare Benefit Policy Manual, Chapter 15, §50 - Drugs and Biologicals. (Accessed August 1, 2022)

Review using the most current Local Coverage Determination (LCD), National Coverage Determination (NCD), or Local Coverage Article (LCA) that applies to the Hawaii region. The LCD, NCD, or LCA can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. Medicare Part B 90-Day Transition Period For new Medicare members, a 90-day transition period applies. During this time, if a member is currently on an active course of the requested treatment, including when furnished by an out-of-network provider, Coverage and Step Therapy do not apply. After the first 90 days of enrollment, Coverage and Step Therapy Criteria must be met for continued coverage. Medicare Part B Step Therapy Criteria

Erythropoietic Stimulating Agents for Cancer Conditions

Updated on: 12/23/2025

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• For new starts, Medicare Part B Step Therapy Criteria must be met in addition to Coverage Criteria before a request may be approved.
• Epogen, Procrit, and Mircera (new starts): The member has an inadequate response to, intolerable adverse event to, or has a contraindication to Retacrit or Aranesp.

Approval Criteria *“ESAs” will be used to refer to all erythropoiesis stimulating agents, unless otherwise specified. Criteria Short Cuts: Medical Necessity Anemia Due to Cancer Chemotherapy Anemia Associated with Myelodysplastic Syndromes (MDS) Anemia Associated with Myeloproliferative Neoplasms

• Myelofibrosis

  Products Aranesp, Epogen, Mircera, Procrit, Retacrit Line of Business Medicaid Approval Length Initial or renewal: 12 months Override Type PA, QL Medical Necessity Criteria: for Medicaid only, for Medicare reviews, refer to the CMS section Treatment with Epogen or Procrit is medically necessary for the indications specified in this policy when one the criteria below are met:

  1. Both of the following: a. History of a trial of adequate dose and duration of Retacrit, resulting in minimal clinical response; AND b. Physician attests that, in their clinical opinion, the clinical response would be expected to be superior to treatment with Retacrit OR
  2. Both of the following: a. History of failure, contraindication, or intolerance to Retacrit; AND b. Physician attests that, in their clinical opinion, the same failure, contraindication, or intolerance would not be expected to occur with Epogen or Procrit

  Products Aranesp, Epogen, Procrit, Retacrit Note: Mircera is unproven for the treatment of anemia due to cancer chemotherapy.29 Diagnosis Anemia Due to Cancer Chemotherapy Line of Business Medicaid & Medicare Approval Length Initial or renewal: 12 months Override Type PA, QL Initial Criteria

  1. Diagnosis of anemia due to cancer chemotherapy; AND
  2. Hematocrit less than or equal to 30% at initiation of therapy; AND
  3. Member does not have evidence of other causes of anemia (e.g., iron deficiency, hemolysis, vitamin B12 deficiency) and there is documentation of normal iron stores; AND
  4. One of the following: a. Member has moderate to severe CKD; OR b. Undergoing palliative treatment; OR c. Receiving myelosuppressive chemotherapy not given with curative intent (i.e., adjuvant therapy or definitive therapy); OR

Erythropoietic Stimulating Agents for Cancer Conditions

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d. Both of the following: 1) Receiving myelosuppressive chemotherapy with curative intent; AND 2) Member is refusing blood transfusion(s) AND

5. Initial authorization will be for no more than 12 months Renewal/Continuation of Therapy Criteria
6. Diagnosis of anemia due to cancer chemotherapy; AND
7. Documentation of positive clinical response to ESA therapy; AND
8. Hematocrit remains less than or equal to 30% for continuation of therapy; AND

9. Reauthorization will be for no more than 12 months NOTE: • Mircera is unproven for the treatment of anemia due to cancer chemotherapy.29 • ESAs are unproven to treat anemia in patients with cancer receiving myelosuppressive chemotherapy when the anticipated outcome is cure (except for patients who refuse blood transfusions).1, 4, 5 • ESAs are unproven to treat anemia in patients with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion.

   Products Aranesp, Epogen, Procrit, and Retacrit Diagnosis Anemia Associated with Myelodysplastic Syndromes (MDS) Line of Business Medicaid & Medicare Approval Length Initial or renewal: 12 months Override Type PA, QL Initial Criteria

10. Diagnosis of Anemia Associated with Myelodysplastic Syndromes (MDS); AND
11. Serum erythropoietin level less than or equal to 500 mUnits/mL; AND
12. Hematocrit is less than or equal to 30% at the initiation of therapy; AND
13. Member does not have evidence of other causes of anemia (e.g., iron deficiency, hemolysis, vitamin B12 deficiency); AND
14. Treatment of lower risk [defined as IPSS-R (Very Low, Low, Intermediate)] disease with symptomatic anemia; AND
15. One of the following: a. Member is with del(5q) chromosomal abnormality;
    OR b. Both of the following: 1) Member is without del(5q) chromosomal abnormality; AND 2) Ring sideroblasts less than 15% (or ring sideroblasts less than 5% with an SF3B1 mutation) OR c. All the following: 1) Member is without del(5q) chromosomal abnormality; AND 2) Ring sideroblasts greater than or equal to15% (or ring sideroblasts greater than or equal to 5% with an SF3B1 mutation); AND 3) Following no response to Reblozyl (luspatercept-aamt) AND
16. Initial authorization will be for no more than 12 months Renewal/Continuation of Therapy Criteria
17. Diagnosis of Anemia Associated with Myelodysplastic Syndromes (MDS); AND
18. Documentation of positive clinical response to ESA therapy; AND
19. Serum erythropoietin level less than or equal to 500 mUnits/mL; AND

Erythropoietic Stimulating Agents for Cancer Conditions

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4. Hematocrit remains less than or equal to 36% for continuation of therapy; AND

5. Reauthorization will be for no more than 12 months

   Products Aranesp, Epogen, Procrit, and Retacrit Diagnosis Anemia Associated with Myeloproliferative Neoplasms - Myelofibrosis Line of Business Medicaid & Medicare Approval Length Initial or renewal: 12 months Override Type PA, QL Initial Criteria

6. Diagnosis of Anemia Associated with Myeloproliferative Neoplasms – Myelofibrosis; AND
7. Serum erythropoietin level less than or equal to 500 mUnits/mL; AND
8. Hematocrit is less than or equal to 30% at the initiation of therapy; AND
9. Member does not have evidence of other causes of anemia (e.g., iron deficiency, hemolysis, vitamin B12 deficiency); AND
10. Initial authorization will be for no more than 12 months Renewal/Continuation of Therapy Criteria
11. Diagnosis of Anemia Associated with Myeloproliferative Neoplasms – Myelofibrosis; AND
12. Documentation of positive clinical response to ESA therapy; AND
13. Serum erythropoietin level less than or equal to 500 mUnits/mL; AND
14. Hematocrit remains less than or equal to 36% for continuation of therapy; AND

15. Reauthorization will be for no more than 12 months

    Additional Information For the purposes of this policy, a conversion factor of 3 should be used to estimate hematocrit when only the hemoglobin is measured, e.g., hemoglobin of 10 g/dL is approximately equal to a hematocrit of 30%, a hemoglobin of 11 g/dL is approximately equal to a hematocrit of 33%, and a hemoglobin of 12 g/dL is approximately equal to a hematocrit of 36%.

    Unproven ESAs are unproven for:1,4-6, 29 • Patients undergoing curative chemotherapy, for information regarding use of ESAs in patients receiving cancer chemotherapy, refer to information in the National Comprehensive Cancer Network (NCCN) Practice Guideline, Cancer- and Chemotherapy-Induced Anemia, as referenced in the Professional Societies section of this policy • Patients with cancer receiving hormonal agents, biologic products or radiotherapy (unless also receiving concomitant myelosuppressive chemotherapy) • Patients with cancer receiving myelosuppressive chemotherapy when the anticipated outcome is cure • Patients with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion Clinical Evidence Oncology Related Anemia Researchers in The Cochrane Collaboration conducted a review of the effect of epoetin and darbepoetin for people with cancer.26 After searching for all relevant studies, they found 91 studies with up to 20,102 people. Trials included in the review consisted of randomized controlled trials on managing anemia in cancer patients receiving or not receiving anti- cancer therapy that compared the use of recombinant human erythropoiesis stimulating agents (ESAs) plus transfusion

Erythropoietic Stimulating Agents for Cancer Conditions

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if needed. Outcomes showed that use of ESAs significantly reduced the relative risk of red blood cell transfusions (risk ratio (RR) 0.65; 95% confidence interval (CI) 0.62 to 0.68, 70 trials, n = 16,093). On average, patients in the ESAs group received one unit of blood less than the control group (mean difference (MD) -0.98; 95% CI -1.17 to -0.78, 19 trials, n = 4,715) and hematological response was observed more often in participants receiving ESAs (RR 3.93; 95% CI 3.10 to 3.71, 31 trials, n = 6,413). There was strong evidence that ESAs increased mortality during the active study period (hazard ratio (HR) 1.17; 95% CI 1.06 to 1.29, 70 trials, n = 15,935) and some evidence that ESAs decreased overall survival (HR 1.05; 95% CI 1.00 to 1.11, 78 trials, n = 19,003). Meta-analyses of patients receiving recombinant human erythropoietin during chemotherapy for lymphoproliferative, lung, and gynecologic malignancies confirmed incremental effectiveness in reducing transfusion requirements, and no significant effects upon either mortality or disease progression.33-34 Researchers found that RR for thromboembolic complications was increased in patients receiving ESAs compared to controls (RR 1.52, 95% CI 1.34 to 1.74; 57 trials, n = 15,498). Additionally, ESAs may have increased the risk for hypertension (fixed-effect model: RR 1.30; 95% CI 1.08 to 1.56; random-effects model: RR 1.12; 95% CI 0.94 to 1.33, 31 trials, n = 7,228) and thrombocytopenia/ hemorrhage (RR 1.21; 95% CI 1.04 to 1.42; 21 trials, n = 4,507). Evidence did not support efficacy of ESA on tumor response (fixed-effect RR 1.02; 95% CI 0.98 to 1.06, 15 trials, n = 5,012). Authors concluded that treatment with ESAs reduced the need for red blood cell transfusions but increased the risk for thromboembolic events and deaths. Evidence suggested that quality of life may be improved with ESAs. Treating providers need to balance the increased risk of death and thromboembolic events against the potential benefits of ESA treatment considering each patient’s clinical circumstances and preferences. More data are needed for the effect of these drugs on quality of life and tumor progression. Further research is warranted to assess cellular and molecular mechanisms and pathways of the effects of ESAs on thrombogenesis and their potential effects on tumor growth. A randomized-placebo-controlled study was conducted to explore the effect on survival and/or disease progression of erythropoietin dosed with higher hemoglobin targets ranges to prevent anemia.1,4,5,11 Women with metastatic breast cancer (n = 939) treated with chemotherapy and using an erythropoietin product received weekly dosing with attempted titration to maintain hemoglobin levels between 12 and 14 g/dL. At four months, death attributed to disease progression was higher (8.7% vs. 3.4%) in women receiving epoetin alfa. There was also a higher rate of fatal thrombotic events in the epoetin group (1.1% vs. 0.2%). Although the study was terminated at that time, Kaplan-Meier estimates of overall survival were significantly lower at 12 months in the epoetin alfa arm (70% vs. 76%). Additionally, decreased locoregional control/progression-free survival, and/or overall survival with erythropoiesis- stimulating agents has been demonstrated in studies of patients with advanced head and neck cancer receiving radiation therapy1,4,5,13 patients receiving chemotherapy for lymphoid malignancy1,4,5, and in patients with non-small cell lung cancer or various malignancies who were not receiving chemotherapy or radiotherapy.1,4,5 The studies of patients with various non-myeloid malignancies not receiving chemotherapy or radiotherapy included a large, phase 3, multicenter, randomized, placebo-controlled trial of 989 patients with hemoglobin (Hgb) ≤ 11 g/dl. The treatment period was 16 weeks. The target hemoglobin in the darbepoetin alfa treatment group was 12-13 g/dL. The final analysis of the initial 16-week treatment period did not show a statistically significant decrease in the proportion of patients receiving red blood cell transfusions. The mean survival was also shorter in the darbepoetin alfa group vs. placebo (8 vs. 10.8 months).1,4,5 A systematic review of randomized, controlled trials of cancer patients showed an increased relative risk of thromboembolic events (RR 1.67, 95% CI, 1.35-2.06) with erythropoiesis-stimulating agents. This review also showed an overall survival hazard ratio of 1.08 (95% CI: 0.99, 1.18).1,4,5,12 Three recent meta-analyses support these findings of increased risk of mortality in patients with cancer receiving ESAs. The relative risks/hazard ratios of mortality in these trials were 1.10 (95% CI, 1.01-1.20)17, 1.17 (95% CI, 1.06-1.30)18, and 1.15 (95% CI, 1.03-1.29)19. Additionally, two analyzed for the relative risks of thromboembolism and reported values of 1.57 (95% CI, 1.31-1.87)26 and 1.69 (95% CI, 1.27-2.24)19. However, two other recent meta-analyses did not find an association between ESAs and increased risk of

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death or disease progression20,21 but did confirm the increased relative risk of thromboembolism: 1.57 (95% CI, 1.10- 2.26)29 and 1.48 (95% CI, 1.28-1.72)21. Agency for Healthcare Research and Quality (US) In 2013, the Agency for Healthcare Research and Quality (AHRQ) conducted an updated systematic review of the comparative benefits and harms of erythropoiesis-stimulating agent (ESA) strategies and non-ESA strategies to manage anemia in patients undergoing chemotherapy and/or radiation for malignancy (excluding myelodysplastic syndrome and acute leukemia), including the impact of alternative thresholds for initiating treatment and optimal duration of therapy.29 Inclusion into the report required enrollment of more than 50 patients per arm in order to avoid potential differential endpoints associated with smaller studies. Results of this update were consistent with the results of the 2006 review. Researchers found: • ESAs reduced the need for transfusions and increased the risk of thromboembolism • Functional Assessment of Cancer Therapy (FACT)-Fatigue scores were better with ESA use, but the magnitude was less than the minimal clinically important difference • An increase in mortality accompanied the use of ESAs • An important unanswered question is whether dosing practices and overall, ESA exposure might influence harms

Professional Societies Cancer- and Chemotherapy-Induced Anemia The NCCN Guidelines for Hematopoietic Growth Factors provide recommendations for the evaluation of Hgb ≤ 11 g/dL or ≥ 2 g/dL below baseline in patients with cancer.6 These guidelines reference the National Cancer Institute (NCI) anemia grading scale of the severity of anemia based on Hgb. Additionally, the NCCN Guidelines for Myelodysplastic Syndromes (MDS) provides recommendations for use of ESA in the management of symptomatic anemia in MDS patients as well as guidelines for Myeloproliferative Neoplasms – Myelofibrosis for management of myelofibrosis- associated anemia.22, 34 Refer to the NCCN’s guidelines for further information. The portions of the guidelines applicable to this policy are:

ESAs are only recommended for anemia due to myelosuppressive chemotherapy for lymphoid malignancies and solid tumors6, for myelodysplastic syndromes, and for myeloproliferative neoplasms,22,34 for anemia associated with myeloid malignancies or acute lymphoblastic leukemia (ALL), refer to NCCN’s guidelines for the condition or appropriate therapy for ALL.

ESAs are not indicated for patients with cancer not receiving therapy, receiving non-myelosuppressive therapy or with an identified, treatable cause of anemia.

For patients with anemia from myelosuppressive chemotherapy, ESAs are not indicated for chemotherapy with curative intent, for anemia due to chemotherapy with a non-curative intent, ESAs may be considered according to FDA-approved indications/dosing/dosing adjustments, and under risk evaluation and mitigation strategy (REMS) guidelines, with informed consent of the patient.

Healthcare providers should counsel each patient on the risk and benefits of ESAs prior to each new course of ESA therapy.

The risks and benefits of ESA therapy versus red blood cell transfusion should be considered.

ESAs may be administered with or without iron supplementation depending on functional iron deficiency status.

ESA therapy should be discontinued following the completion of a chemotherapy course or when a loss in response is identified. ESAs should be permanently discontinued in patients with antibody-mediate anemia.

Initial dosing, monitoring and dosage adjustments based on Hgb levels are recommended according to the manufacturer’s product information or alternative regimens detailed in the guideline.6,22,34

Erythropoietic Stimulating Agents for Cancer Conditions

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o ESAs may be used in patients with del(5q) and symptomatic anemia where serum epo levels are ≤ 500 mU/mL.

For cancer with chronic kidney disease, consider treatment with ESAs according to FDA indications and dosing for chronic kidney disease, risk versus benefit evaluation is required, CKD patients not receiving active therapy for a malignancy should try to avoid ESAs, while those receiving palliative chemotherapy may favor ESAs over transfusion for severe anemia. A CKD patient with a curable solid tumor should not receive ESAs during chemotherapy, but they may be utilized with caution after chemotherapy is complete.

Studies have reported possible decreased survival in cancer patients receiving ESAs. Analyses of eight studies in patients with cancer found decreased survival with ESAs when anemia was corrected to a target Hgb level of > 12 g/dL. However, the shortened survival and tumor progression risks have not been excluded when ESAs are dosed to a target Hgb < 12 g/dL. Also, three meta-analysis updates on survival indicate increased risk of mortality with use of ESAs. However, two meta-analyses did not show significant effect on mortality or disease progression with ESA use. ESA’s may be used in the management of symptomatic anemia in myelodysplastic syndromes with a treatment target hemoglobin ≤ 12 g/dL. Recent pharmacovigilance trials have reported no adverse effects on survival in cancer patients with chemotherapy-induced anemia receiving ESAs.22

US Food and Drug Administration (FDA) This section is to be used for informational purposes only. FDA approval alone is not a basis for coverage. Drug Name Indication Epogen, Procrit, and Retacrit (epoetin alfa biosimilar) treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and patients not on dialysis; treatment of anemia in zidovudine-treated HIV-infected patients; treatment of anemia in cancer patients on concomitant myelosuppressive chemotherapy and upon initiation, there is a minimum of two additional months of planned chemotherapy; and in reduction of the need for allogeneic blood transfusion in noncardiac, nonvascular, elective surgery patients.4,5,26 Aranesp Treatment of anemia associated with chronic kidney disease (CKD), including patients on dialysis and patients not on dialysis; and for the treatment of anemia in cancer patients on concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy.1

The prescribing information for darbepoetin alfa, epoetin alfa, and MPG-epoetin beta contains a warning regarding reports of pure red cell aplasia (PRCA) and severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin. This warning states that any patient who develops a sudden loss of response, accompanied by severe anemia and low reticulocyte count should be evaluated for the etiology of loss of effect, including the presence of neutralizing antibodies to erythropoietin. If anti-erythropoietin antibody-associated anemia is suspected, ESAs should be withheld and the manufacturer contacted as directed in the prescribing information to perform assays for binding and neutralizing antibodies.1,4,5,29 A biosimilar product is a biologic product that is approved based on demonstrating that it is highly similar to an FDA‐ approved biologic product, known as a reference product, and has no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products. The chart below highlights the white blood cell colony stimulating factor reference products and respective biosimilar product. References

1. Aranesp® [prescribing information]. Thousand Oaks, CA: Amgen Inc., April 2024.
2. Musto P, Lanza F, BValleari E, Grossi A, Flacone A, et al. Darbepoetin alpha for the treatment of anaemia in low intermediate risk myelodysplastic syndromes. Br J Haematol. 2005; 128 (2): 204-9.

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3. Steurer M, Sudmeier I, Stauder R, Gastl G. Thromboembolic events in patients with myelodysplastic syndrome receiving thalidomide in combination with darbepoetin-alpha. Br J Haematol. 2003 April. 121(1): 101-3.
4. Procrit® [prescribing information]. Horsham, PA: Janssen Products, LP, April 2024.
5. Epogen® [prescribing information]. Thousand Oaks, CA: Amgen Inc., April 2024.
6. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines™): Hematopoietic Growth Factors. V1.2025. Available at www.nccn.org. Accessed February 10, 2025.
7. Ferrini, P.A., Grossi, A. et al. Br J Haematol. A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes. 1998 Dec; 103(4):1070-4.
8. Thompson JA, Gilliland DG et al. Effect of recombinant human erythropoietin combined with granulocyte/macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. GM/EPO MDS Study Group. Blood. 2000 Feb 15;95(4): 1175-9.
9. Leyland-Jones B, Semiglazov V, Pawlicki M, et al. Maintaining Normal Hemoglobin Levels With Epoetin Alfa in Mainly Nonanemic Patients with Metastatic Breast Cancer Receiving First-Line Chemotherapy: A Survival Study. JCO. 2005;23(25):1-13.
10. Bohlius J, Wilson J, Seidenfeld J, et al. Recombinant Human Erythropoietins and Cancer Patients: Updated Meta- Analysis of 57 Studies including 9353 Patients. J Natl Cancer Inst. 2006;98(10):708-14.
11. Henke M, Laszig R, Rube C, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomized, double-blind, placebo-controlled trial. The Lancet. 2003;362(9392):1255-60.
12. Gouva C, Nikolopoulos P, Ioannidis JP, Siamopoulos KC. Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial. Kidney Int. 2004;66(2):753-60.
13. Rossert J, Levin A, Roger SD, et al. Effect of early correction of anemia on the progression of CKD. Am J Kidney Dis. 2006;47(5):738-750.
14. Unger EF, Thompson AM, Blank MJ, Temple R. Erythropoiesis Stimulating Agents—Time for a Reevaluation. N Eng J Med. 2010;362(3):189-92.
15. Bennett CL, Silver SM, Djulbegovic B, et al. Venous Thromboembolism and Mortality Associated With Recombinant Erythropoietin and Darbepoetin Administration for the Treatment of Cancer-Associated Anemia. JAMA. 2008;299(8):914-24.
16. Bohlius J, Schmidlin K, Brillant C, et al. Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet. 2009;373(9674):1532-42.
17. Tonelli M, Hemmelgarn B, Reiman T, et al. Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis. CMAJ. 2009;180(11):E62-71.
18. Ludwig H, Crawford J, Osterborg A, et al. Pooled Analysis of Individual Patient-Level Data From All Randomized, Double-Blind, Placebo-Controlled Trials of Darbepoetin Alfa in the Treatment of Patients With Chemotherapy- Induced Anemia. 2009;27(17):2838-47.
19. Glaspy J, Crawford J, Vansteenkiste J, et al. Erythropoiesis-stimulating agents in oncology: a study-level meta- analysis of survival and other safety outcomes. Br J Cancer. 2010;102(2):301-15.
20. U.S. Food and Drug Administration. October 18, 2010: Cardiovascular and Renal Drugs Advisory Committee Meeting Announcement.
21. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines™): Myelodysplastic Syndromes. v2.2025. Available at www.nccn.org. Accessed February 10, 2025.
22. Dietrich DT, Wasserman R, Bräu, et al. Once-weekly epoetin alfa improves anemia and facilities maintenance of ribavirin dosing in hepatitis C virus-infected patient receiving ribavirin plus interferon alfa. Am J Gastroenterol. 2003;98(11):249-9.
23. Afdahal NH, Dieterich DT, Pockros PJ, et al. Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective, double-blind, randomized controlled study. Gastroenterology. 2004;126(5):1302-11.
24. Retacrit™ [prescribing information]. New York, NY: Pfizer Inc., June 2024.

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25. Hahn D, Esezobor CI, Elserafy N, et al. Short-acting erythropoiesis-stimulating agents for anaemia in predialysis patients. Cochrane Database Syst Rev. 2017 Jan 9;1:CD011690.
26. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012 Aug;2(4):279-335.
27. Grant MD, Piper M, Bohlius J,et al. Epoetin and darbepoetin for managing anemia in patients undergoing cancer treatment: comparative effectiveness update [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013 Apr. Report No.:13-EHC077-EF. AHRQ Comparative Effectiveness Reviews.
28. Mircera® [prescribing information]. South San Francisco, CA: Hoffman-La Roche Inc., June 2024.
29. Saglimbene VM, Palmer SC, Ruospo M, et al. Continuous erythropoiesis receptor activator (CERA) for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2017 Aug 7;8:CD009904.
30. Mesgarpour B, Heidinger BH, Roth D, et al. Harms of off-label erythropoiesis-stimulating agents for critically ill people. Cochrane Database Syst Rev. 2017 Aug 25;8:CD010969.
31. Hedenus M, Osterborg A, Tomita D, Bohac C, Coiffier B. Effects of erythropoiesis-stimulating agents on survival and other outcomes in patients with lymphoproliferative malignancies: a study-level meta-analysis. Leukemia and Lymphoma 2012;53(11):2151-8. DOI: 10.3109/10428194.2012.684347. [Context Link 1] View abstract.
32. Ohashi Y, et al. Meta-analysis of epoetin beta and darbepoetin alfa treatment for chemotherapy-induced anemia and mortality: Individual patient data from Japanese randomized, placebo-controlled trials. Cancer Science 2013;104(4):481-5. DOI: 10.1111/cas.12105.
33. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines™): Myeloproliferative Neoplasms - Myelofibrosis. V2.2025. Available at www.nccn.org. Accessed September 18, 2025.
34. Cervantes F, Alvarez-Larran A, Hernandez-Boluda JC, et al. Darbepoetin-alpha for the anaemia of myelofibrosis with myeloid metaplasia. Br J Haematol 2006;134:184-186.

35. Tsiara SN, Chaidos A, Bourantas LK, et al. Recombinant human erythropoietin for the treatment of anaemia in patients with chronic idiopathic myelofibrosis. Acta Haematol 2007;117:156-161.

    Review History 11/26/2025 – adopted ESA for Oncology (Optum Health’s criteria).