Key facts for NCD 110.21
- Benefit category
- Drugs and Biologicals
- Effective date
- 07/30/2007
- Implemented 04/07/2008
- Transmittal
- Transmittal 80
- Versions published
- 1
- Manual chapter
- 110
- NCD Manual (Pub. 100-03)
TL;DR
NCD 110.21 sets Medicare's national policy for erythropoiesis stimulating agents (esas) in cancer and related neoplastic conditions under the benefit category "Drugs and Biologicals", effective 07/30/2007 and implemented 04/07/2008. 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: It has been revised once since publication and binds every Medicare Administrative Contractor nationally.
Item or service described
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.
Indications and limitations of coverage
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 1g/dl (hematocrit > 3%) over 2 weeks of treatment unless the hemoglobin remains below or subsequently falls to
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 Medicare Administrative Contractors 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.
Text reproduced from the CMS Medicare Coverage Database record for NCD 110.21 version 1. View the original on cms.gov.
Revision history
10/2024 - The purpose of the Change Request (CR) is to provide a quarterly maintenance update of ICD-10 coding conversions and other coding updates specific to National Coverage Determinations(NCDs). No policy is being changed as a result of these updates. ( TN 12903 ) (CR13818)
01/2021 - Transmittal 10515, dated December 10, 2020, is being rescinded and replaced by Transmittal 10566, dated, January 14, 2021 to remove FISS Reason Codes (RCs) 59041, 59042, 59209, and 59210 from the spreadsheet for NCD 160.18. All other information remains the same. ( TN 10566 ) (CR12027)
12/2020 - This Change Request (CR) constitutes a maintenance update of ICD-10 conversions and other coding updates specific to NCDs. These NCD coding changes are the result of newly available codes, coding revisions to NCDs released separately, or coding feedback received.
Previous NCD coding changes appear in ICD-10 quarterly updates that can be found at: https://www.cms.gov/Medicare/Coverage/CoverageGenInfo/ICD10.html , along with other CRs implementing new policy NCDs. Edits to ICD-10 and other coding updates specific to NCDs will be included in subsequent quarterly releases and individual CRs as appropriate. No policy-related changes are included with the ICD-10 quarterly updates. Any policy-related changes to NCDs continue to be implemented via the current, longstanding NCD process. ( TN 10515 ) (CR12027)
10/2020 - This Change Request (CR) constitutes a maintenance update of ICD-10 conversions and other coding updates specific to NCDs. These NCD coding changes are the result of newly available codes, coding revisions to NCDs released separately, or coding feedback received.
Previous NCD coding changes appear in ICD-10 quarterly updates that can be found at: https://www.cms.gov/Medicare/Coverage/CoverageGenInfo/ICD10.html , along with other CRs implementing new policy NCDs. Edits to ICD-10 and other coding updates specific to NCDs will be included in subsequent quarterly releases and individual CRs as appropriate. No policy-related changes are included with the ICD-10 quarterly updates. Any policy-related changes to NCDs continue to be implemented via the current, longstanding NCD process. ( TN 10432 ) (CR12027)
11/2018 - This Change Request (CR) constitutes a maintenance update of ICD-10 conversions and other coding updates specific to NCDs. These NCD coding changes are the result of newly available codes, coding revisions to NCDs released separately, or coding feedback received.
Previous NCD coding changes appear in ICD-10 quarterly updates that can be found at: https://www.cms.gov/Medicare/Coverage/CoverageGenInfo/ICD10.html , along with other CRs implementing new policy NCDs. Edits to ICD-10 and other coding updates specific to NCDs will be included in subsequent quarterly releases and individual CRs as appropriate. No policy-related changes are included with the ICD-10 quarterly updates. Any policy-related changes to NCDs continue to be implemented via the current, long-standing NCD process.( TN 2202 ) (CR11005)
11/2018 - This Change Request (CR) constitutes a maintenance update of ICD-10 conversions and other coding updates specific to NCDs. These NCD coding changes are the result of newly available codes, coding revisions to NCDs released separately, or coding feedback received.
Previous NCD coding changes appear in ICD-10 quarterly updates that can be found at: https://www.cms.gov/Medicare/Coverage/CoverageGenInfo/ICD10.html , along with other CRs implementing new policy NCDs. Edits to ICD-10 and other coding updates specific to NCDs will be included in subsequent quarterly releases and individual CRs as appropriate. No policy-related changes are included with the ICD-10 quarterly updates. Any policy-related changes to NCDs continue to be implemented via the current, long-standing NCD process.( TN 2200 ) (CR10859)
09/2018 - This Change Request (CR) constitutes a maintenance update of ICD-10 conversions and other coding updates specific to NCDs. These NCD coding changes are the result of newly available codes, coding revisions to NCDs released separately, or coding feedback received.
Previous NCD coding changes appear in ICD-10 quarterly updates that can be found at https://www.cms.gov/Medicare/Coverage/CoverageGenInfo/ICD10.html , along with other CRs implementing new policy NCDs. Edits to ICD-10 and other coding updates specific to NCDs will be included in subsequent quarterly releases and individual CRs as appropriate. No policy-related changes are included with the ICD-10 quarterly updates. Any policy-related changes to NCDs continue to be implemented via the current, long-standing NCD process.( TN 2138 ) (CR10859)
08/2018 - This Change Request (CR) constitutes a maintenance update of ICD-10 conversions and other coding updates specific to NCDs. These NCD coding changes are the result of newly available codes, coding revisions to NCDs released separately, or coding to feedback received.
Previous NCD coding changes appear in ICD-10 quarterly updates that can be found at: https://www.cms.gov/Medicare/Coverage/CoverageGenInfo/ICD10.html , along with other CRs implementing new policy NCDs. Edits to ICD-10 and other coding updates specific to NCDs will be included in subsequent quarterly releases and individual CRs as appropriate. No policy-related changes are included with the ICD-10 quarterly updates. Any policy-related changes to NCDs continue to be implemented via the current, long-standing NCD process. ( TN 2122 ) (CR10859)
02/2018 - Transmittal 2033, dated February 16, 2018, is being rescinded and replaced by Transmittal 2039, dated, February 28, 2018 to correct instructions in business requirement 7, NCD210.3, Colorectal Cancer Screening, and its accompanying spreadsheet. All other information remains the same. ( TN 2039 ) (CR10473)
02/2018 - This Change Request (CR) constitutes a maintenance update of International Code of Diseases, Tenth Revision (ICD-10) conversions and other coding updates specific to National Coverage Determinations (NCDs). These NCD coding changes are the result of newly available codes, coding revisions to NCDs released separately, or coding feedback received.
Previous NCD coding changes appear in ICD-10 quarterly updates that can be found at: https://www.cms.gov/Medicare/Coverage/CoverageGenInfo/ICD10.html , along with other CRs implementing new policy NCDs. Edits to ICD-10 and other coding updates specific to NCDs will be included in subsequent quarterly releases and individual CRs as appropriate. No policy-related changes are included with the ICD-10 quarterly updates. Any policy-related changes to NCDs continue to be implemented via the current, long-standing NCD process. ( TN 2033 ) (CR10473)
01/2018 - This Change Request (CR) constitutes a maintenance update of International Code of Diseases, Tenth Revision (ICD-10) conversions and other coding updates specific to National Coverage Determinations (NCDs). These NCD coding changes are the result of newly available codes, coding revisions to NCDs released separately, or coding feedback received.
Previous NCD coding changes appear in ICD-10 quarterly updates that can be found at: https://www.cms.gov/Medicare/Coverage/CoverageGenInfo/ICD10.html , along with other CRs implementing new policy NCDs. Edits to ICD-10 and other coding updates specific to NCDs will be included in subsequent quarterly releases and individual CRs as appropriate. No policy-related changes are included with the ICD-10 quarterly updates. Any policy-related changes to NCDs continue to be implemented via the current, long-standing NCD process. ( TN 2005 ) (CR10318)
11/2017 - This Change Request (CR) constitutes a maintenance update of International Code of Diseases, Tenth Revision (ICD-10) conversions and other coding updates specific to National Coverage Determinations (NCDs). These NCD coding changes are the result of newly available codes, coding revisions to NCDs released separately, or coding feedback received. ( TN 1975 ) (CR10318)
How this NCD shows up on remittances
A service denied under a National Coverage Determination returns CARC 50 (not deemed medically necessary) with remark N386 (decision based on an NCD); a denial citing a local policy instead carries N115. Because NCDs bind nationally, the appeal path is documentation that the patient meets the indications above, not a contractor-policy argument.
How QuickIntell applies NCD 110.21
QuickAuth checks the ordered service and diagnosis against NCD and LCD criteria before the encounter, QuickCode validates the diagnosis pairing on the claim, and QuickRCM routes CARC 50 denials with the policy text and the covered-code list attached so the appeal starts with evidence.
Frequently asked questions — NCD 110.21
What does NCD 110.21 cover?
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 full indications and limitations are reproduced on this page from the CMS Medicare Coverage Database.
When did NCD 110.21 take effect?
The current version (1) is effective 07/30/2007, implemented 04/07/2008, published in transmittal 80. This is the only published version.
Does a Local Coverage Determination override NCD 110.21?
No. A National Coverage Determination binds all Medicare Administrative Contractors; an LCD can only address services or circumstances the NCD leaves open. Claims denied under this NCD typically return CARC 50 with remark N386 (NCD) rather than N115 (LCD).
Sources
Every figure on this page is taken from the CMS publications below, as released by the Centers for Medicare & Medicaid Services. Projection built 2026-10-02. Verify against the primary file before billing or contracting decisions.
- Medicare Coverage Database NCDs via the CMS Coverage APIVersion API snapshot 2026-09-27 · effective 2026-09-20 · file national-coverage-ncd.jsonSHA-256 a90fadfd264b9ef4…
Disclaimer
This page reproduces the CMS National Coverage Determination text and, for laboratory NCDs, the CMS ICD-10 edit lists, as an operational reference. Coverage decisions depend on the full policy, the claim and the contractor; nothing here is legal, clinical or billing advice. CPT codes are shown as numbers only; CPT descriptors are copyright AMA.