(Medicare National Coverage Determinations Manual)

D. Other   A/B MACs may determine coverage for other all -oral three -drug antiemesis regimens of aprepitant or any other FDA approved oral NK -1 antagonist in combination with an oral 5HT3 antagonist and oral dexamethasone with the chemotherapeutic agents listed above, or any other anticancer chemotherapeutic agents that are FDA approved and are defined as highly or moderately emetogenic.   (Last reviewed May 2013.)   110.19  Abarelix for the Treatment of Prostate Cancer (RETIRED)  (Rev. 11892; Issued: 03- 09-23; Effective: 04 -10-23; Implementation:04- 10-23)    Effective January 1, 2021, the Centers for Medicare & Medicaid Services determined that no national coverage determination  (NCD)  is appropriate  at this time for Abarelix  for the Treatment  of Prostate  Cancer. In the absence of an NCD, coverage determinations will be made by the Medicare Administrative Contractors under 1862(a)(1)(A) of the Social Security Act.   110.20 - Blood Brain Barrier Osmotic Disruption for Treatment of Brain Tumors (Effective March 20, 2007)  (Rev. 67, Issued:  04- 06-07; Effective Date:  03 -20-07; Implementation Date:  05 -07-07)  A. General   The blood brain barrier (BBB) of the central nervous system is characterized by tight junctions between vascular endothelial cells, which prevent or impede various naturally occurring and synthetic substances (including anti -cancer drugs) from entering bra in tissue.  The BBB may be partly responsible for the poor efficacy of chemotherapy for malignant primary or metastatic brain tumors.   The BBBD is the disruption of the tight junctions between the endothelial cells that line the capillaries in the brain accomplished by osmotic disruption, bradykinin or irradiation.  Theoretically, disruption of the BBB may, in the treatment of brain tumor s, increase the concentration of chemotherapy drugs delivered to the tumor and may prolong the drug- tumor contact time.   Osmotic disruption of the BBB is the most common technique used.  Chemotherapeutic agents are given in conjunction with barrier disruption.  The BBBD process includes all items and services necessary to perform the procedure, including hospitalization, monitoring, and repeated imaging procedures.   B. Nationally Covered Indications   N/A  C. Nationally Non -Covered Indications   Effective for services performed on and after March 20, 2007, the Centers for Medicare & Medicaid Services determines that the use of osmotic BBBD is not reasonable and necessary when it is used as part of a treatment regimen for brain tumors.   D. Other  This NCD does not alter in any manner the coverage of anti- cancer chemotherapy.   (This NCD last reviewed March 2007.)  110.21  - Erythropoiesis Stimulating Agents (ESAs) in Cancer and Related Neoplastic 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 st arting 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.   110.22 - Autologous Cellular Immunotherapy Treatment (Effective June 30, 2011)  (Rev. 140, Issued: 01- 06-12, Effective: 06 -30-11, Implementation: 08- 08-11)  A. General   Prostate cancer is the most common non- cutaneous cancer in men in the United States.  In 2009, an estimated 192,280 new cases of prostate cancer were diagnosed and an estimated 27,360 deaths were reported.  The National Cancer Institute states that prostat e cancer is predominantly a cancer of older men; the median age at diagnosis is 72 years.  Once the patient has castration -resistant, metastatic prostate cancer the median survival is generally less than two years.  In 2010 the Food and Drug Administration (FDA) approved sipuleucel -T (PROVENGE; APC8015), for patients with castration -resistant, metastatic prostate cancer.  The posited mechanism of action, immunotherapy, is different from that of anti -cancer chemotherapy such as docetaxel.  This is the first immunotherapy for prostate cancer to receive FDA approval.   The goal of immunotherapy is to stimulate the body's natural defenses (such as the white blood cells called dendritic cells, T -lymphocytes and mononuclear cells) in a specific manner so that they attack and destroy, or at least prevent, the proliferation of cancer cells.  Specificity is attained by intentionally exposing a patient's white blood cells to a particular protein (called an antigen) associated with the prostate cancer.  This exposure "trains" the white blood cells to target and attack the prostat e cancer cells.  Clinically, this is expected to result in a decrease in the size and/or number of cancer sites, an increase in the time to cancer progression, and/or an increase in survival of the patient.  Sipuleucel -T differs from other infused anti -cancer therapies.  Most such anti -cancer therapies are manufactured and sold by a biopharmaceutical company and then purchased by and dispensed from a pharmacy.  In contrast, once the decision is made to treat w ith sipuleucel -T, a multi- step process is used to produce sipuleucel -T.  Sipuleucel -T is made individually for each patient with his own white blood cells.  The patients white blood cells are removed via a procedure called leukapheresis.  In a laboratory the white blood cells are exposed to PA2024, which is a molecule created by linking prostatic acid phosphatase (PAP) with granulocyte/macrophage -colony stimulating factor (GM -CSF).  PAP is an antigen specifically associated with prostate cancer cells; GM -CSF is a protein that targets a receptor on the surface of white blood cells.  Hence, PAP serves to externally manipulate the immunological functioning of the patient's white blood cells while GM -CSF serves to stimulate the white blood cells into action.  As  noted in the FDA's clinical review, each dose of sipuleucel -T contains a minimum of 40 million treated white blood cells, however there is "high inherent variability" in the yield of sipuleucel -T from leukapheresis to leukapheresis in the same patient as well as from patient to patient.  The treated white blood cells are then infused back into the same patient.  The FDA -approved dosing regimen is three doses with each dose administered two weeks apart.   Indications and Limitations of Coverage   B. Nationally Covered Indications   Effective for services performed on or after June 30, 2011, The Centers for Medicare and Medicaid Services (CMS) proposes that the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment -  sipuleucel -T; PROVENGE improv es health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate -resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for this on- label indication under 1862(a)(1)(A) of the Social  Security Act.  C. Nationally Non -Covered Indications   N/A  D. Other  Effective for services performed on or after June 30, 2011, coverage of all off -label uses of autologous cellular immunotherapy treatment  sipuleucel -T; PROVENGE for the treatment of prostate cancer is left to the discretion of the local A/B MACs .  (NCD last reviewed June 2011.)   110.23 - Stem Cell Transplantation (Formerly 110.8.1) (Various Effective Dates Below)  (Rev. 193, Issued; 07- 01-16, Effective: 01 -27-16, Implementation: 10- 03-16)  A. General   Stem cell transplantation is a process in which stem cells are harvested from either a patients (autologous) or donors (allogeneic) bone marrow or peripheral blood for intravenous infusion.  Autologous stem cell transplantation (AuSCT) is a technique for restoring stem cells using the patient's own previously stored cells. AuSCT  must be used to effect hematopoietic reconstitution following severely myelotoxic doses of chemotherapy (HDCT) and/or radiotherapy used to treat various malignancies.  Allogeneic hematopoietic stem cell transplantation (HSCT) is a procedure in which a portion of a healthy donor's stem cell or bone marrow is obtained and prepared for intravenous infusion.  Allogeneic HSCT  may be used to restore function in recipients having an inherited or acquired deficiency or defect.  Hematopoietic stem cells are multi- potent stem cells that give rise to all the blood cell types; these stem cells form blood and immune cells.  A hematopoietic stem cell is a cell isolated from blood or bone marrow that can renew itself, differentiate to a variety of specialized cells , can mobilize out of the bone marrow into circulating blood, and can undergo programmed cell death, called apoptosis -  a process by which cells that are unneeded or detrimental will self -destruct.