CMS Pub. 100-03, ch. 1, § 110.21

Conditions

(Rev. 173, Issued: 09-04-14, Effective: Upon Implementation: of ICD-10, Implementation: Upon Implementation of ICD-10)

A. General

Erythropoiesis stimulating agents (ESAs) stimulate the bone marrow to make more red blood cells and are

United States Food and Drug Administration (FDA) approved for use in reducing the need for blood

transfusion in patients with specific clinical indications. The FDA has issued alerts and warnings for ESAs

administered for a number of clinical conditions, including cancer. Published studies report a higher risk of

serious and life-threatening events associated with oncologic uses of ESAs.

B. Nationally Covered Indications

ESA treatment for the anemia secondary to myelosuppressive anticancer chemotherapy in solid tumors,

multiple myeloma, lymphoma, and lymphocytic leukemia is only reasonable and necessary under the

following specified conditions:

• The hemoglobin level immediately prior to initiation or maintenance of ESA treatment is <10 g/dL (or

the hematocrit is <30%).

• The starting dose for ESA treatment is the recommended FDA label starting dose, no more than 150

U/kg/3 times weekly for epoetin and 2.25 mcg/kg/1 time weekly for darbepoetin alpha. Equivalent doses

may be given over other approved time periods.

• Maintenance of ESA therapy is the starting dose if the hemoglobin level remains below 10g/dL (or

hematocrit is <30%) 4 weeks after initiation of therapy and the rise in hemoglobin is >1g/dL (hematocrit

>3%);

• For patients whose hemoglobin rises <1g/dl (hematocrit rise <3%) compared to pretreatment baseline

over 4 weeks of treatment and whose hemoglobin level remains <10g/dL after the 4 weeks of treatment

(or the hematocrit is <30%), the recommended FDA label starting dose may be increased once by 25%.

Continued use of the drug is not reasonable and necessary if the hemoglobin rises <1g/dl (hematocrit rise

<3%) compared to pretreatment baseline by 8 weeks of treatment.

• Continued administration of the drug is not reasonable and necessary if there is a rapid rise in

hemoglobin >1g/dl (hematocrit >3%) over 2 weeks of treatment unless the hemoglobin remains below or

subsequently falls to <10g/dL (or the hematocrit is <30%). Continuation and reinstitution of ESA

therapy must include a dose reduction of 25% from the previously administered dose.

• ESA treatment duration for each course of chemotherapy includes the 8 weeks following the final dose

of myelosuppressive chemotherapy in a chemotherapy regimen.

C. Nationally Non-Covered Indications

ESA treatment is not reasonable and necessary for beneficiaries with certain clinical conditions, either

because of a deleterious effect of the ESA on their underlying disease or because the underlying disease

increases their risk of adverse effects related to ESA use. These conditions include:

• Any anemia in cancer or cancer treatment patients due to folate deficiency, B-12 deficiency, iron

deficiency, hemolysis, bleeding, or bone marrow fibrosis;

• The anemia associated with the treatment of acute and chronic myelogenous leukemias (CML,

AML), or erythroid cancers;

• The anemia of cancer not related to cancer treatment;

• Any anemia associated only with radiotherapy;

• Prophylactic use to prevent chemotherapy-induced anemia;

• Prophylactic use to reduce tumor hypoxia;

• Patients with erythropoietin-type resistance due to neutralizing antibodies; and

• Anemia due to cancer treatment if patients have uncontrolled hypertension.

D. Other

Local A/B MACs may continue to make reasonable and necessary determinations on all other uses of ESAs

not specified in this National Coverage Determination.

See the Medicare Benefit Policy Manual, chapter 11, section 90 and chapter 15, section 50.5.2 for coverage

of ESAs for end-stage renal disease-related anemia.