Article - Billing and Coding: Erythropoiesis Stimulating Agents (A58982)

Anemia Due to Antineoplastic ChemotherapyThis policy does not replace or supersede existing Medicare applicable National Coverage Determination (NCD) 110.21.Epoetin beta is NOT indicated or covered for treatment of anemia due to cancer chemotherapy.Required Documentation Elements:The ESA utilized:Darbepoetin alfa (J0881) or epoetin alfa (J0885) or epoetin alfa-epbx biosimilar (Q5106)Use of the ESA forsymptomaticanemia due to antineoplastic chemotherapyA diagnosis of a non-myeloid malignancy (solid tumor, multiple myeloma, lymphoma, or lymphocytic leukemia)For HCPCS codes J0881, J0885 or Q5106: ICD-10-CM code D64.81 or D61.810 AND 1 of the malignancy codes listed in ICD-10 Group 3 MUST be billed together. The EA modifier is also required. A JA or JB modifier is required.Inclusion of any other ICD-10 diagnoses on the claim which are non-covered with an EC modifier per NCD 110.21, except for ICD-10 codes strictly indicating a relationship to adverse effect of antineoplastic drugs or chemotherapy, will preclude payment for the ESA.DOSING:Fordarbepoetin alfa therapy in anemia due to antineoplastic chemotherapy:2.25 mcg/kg every week SQ or 500 mcg every 3 weeks until completion of the chemotherapy course.If Hb increases more than 1 g/dL in any 2-week period or if a Hblevel is reached that will avoid RBC transfusion, then the dose of darbepoetin alfa should be decreased by 40%.During treatment, if Hbincreases by less than 1 g/dLandremains below 10 g/dL after 4 weeks of therapy, the dose of darbepoetin alfa may be increased once by 25%.If there is no response as measured by Hblevels or if RBC transfusions are still required after 8 weeks of therapy, darbepoetin therapy should be stopped. Darbepoetin therapy must cease following completion of a chemotherapy course.Forepoetin alfa/epoetin alfa-epbx biosimilar in anemia due to antineoplastic chemotherapy:Initial dosing:150 Units/kg SC TIW or 40,000 units SC weeklyReduce dose by 25% when Hbreaches a level needed to avoid transfusion or increases > 1 g/dL in any 2-week period.Increase dose by 25%, if there is no reduction in transfusion requirements or the Hblevel does not rise>1 g/dL after 4 weeks of therapy.If after 8 weeks of therapy there is no response as measured by Hblevels or if transfusions are still required, epoetin alfa should be discontinued. Epoetin alfa therapy must cease following completion of a chemotherapy course.ESA treatment duration for each course of chemotherapy includes the 8 weeks following the final dose of myelosuppressive chemotherapy in a chemotherapy regimen.Any ESA administered for anemia in association with cancer chemotherapy will only be covered if the Hb level immediately prior to initiation or maintenance of the ESA treatment is less than 10 g/dL (or the HCT < 30%).An ESA should only be started if there is a minimum of 2 additional months of planned chemotherapy.ESAs should not be used in a patient with cancer receiving myelosuppressive chemotherapy when the anticipated outcome for the cancer is cure.Hb levels should be monitored on a weekly basis in patients receiving ESA therapy until Hb becomes stable. ESA doses should be titrated as low as possible for each patient to achieve and maintain the lowest Hblevel sufficient to avoid the need for blood transfusion.Although no specific serum EPO level can be stipulated above which patients would be unlikely to respond to ESA therapy, treatment of patients with grossly elevated serum EPO levels (e.g., > 200 mUnits/mL) is not recommended.Evaluation and treatment of other causes of anemia must occur pre-ESA initiation and at any time thereafter as needed for lack of responsiveness.Prior to ESA therapy, the patients iron stores, including transferrin saturation (serum iron divided by iron binding capacity) and serum ferritin, must be evaluated. Transferrin saturation should be at least 20%, and ferritin should be at least 100 ng/mL. Iron stores must also be checked prior to dosage increases. Even without dosage adjustments, iron storage must be checked at least every 3 months during ongoing ESA therapy.If the initial dose of an ESA was administered in another setting (i.e., hospital, in a state outside our jurisdiction, or in another facility); subsequent office-administered ESAs must still meet all the above-mentioned requirements. This may require review of outside medical records and confirmation that needed pre-treatment lab results and evaluation were completed appropriately.Anemia in Zidovudine Treated HIV InfectionDarbepoetin alfa and epoetin beta are NOT indicated for this condition.Forepoetin alfa/epoetin alfa-epbx biosimilar in anemia related to Zidovudine treated HIV:Epoetin alfa is not indicated for the treatment of anemia in HIV-infected patients due to other factors such as iron or folate deficiencies, hemolysis, or gastrointestinal bleeding, which should be managed appropriately.Epoetin alfa therapy for anemia related to Zidovudine therapy for HIV must not target a Hb> 12 g/dL.Required Documentation Elements:Use of the ESA forsymptomaticanemia due to AZT therapyZidovudine therapy at a dose<4200 mg/weekAn endogenous baseline pre-transfusion serum EPO level<500 mUnits/mLA dose titrated to the individual need to achieve and maintain the lowest Hb level needed to avoid RBC transfusions.The ESA Utilized:Epoetin alfa (J0885) or epoetin alfa-epbx biosimilar (Q5106)For patients with symptomatic anemia due to adverse impact of AZT, a diagnosis of D61.1 and either B20 or B97.35 must be billed with HCPCS codes J0885 or Q5106.A JA or JB modifier is required.The EC modifier is also required.Inclusion of any other ICD-10 diagnoses on the claim which are non-covered with an EC modifier per NCD 110.21, will preclude payment for the ESA.DOSING:Initial dosing: 100 Units/kg TIW for 8 weeks.Maintenance dosing: After 8 weeks of initial therapy, if the response has not been satisfactory in terms of decreasing RBC transfusion or the Hblevel, then the dose may be increased by 50-100 units/kg TIW.Response should be evaluated and documented every 4-8 weeks thereafter with the dose adjusted accordingly by 50 to 100 Units/kg increments TIW. If the Hb exceeds 12 g/dL then the ESA should be stopped until the Hbdrops below 11 g/dL at which time it can be restarted at a dose reduced by at least 25%. During maintenance, dosage variations will depend on the presence of intercurrent infections and variances in Zidovudine dosing.Dosing should never exceed 300 units/kg TIW as further improvements in response are unlikely.For Anemia in Myelodysplastic Syndromes (MDS)MDS comprises a range of hematologic malignancies characterized by isolated or multiple cytopenias accompanied by abnormal cellular maturation. Much of the morbidity and death from MDS is due to the cytopenia impacts rather than transformation to acute myeloid leukemia (AML). There are well supported scenarios in which ESAs can be used as part of the therapeutic regimen in a very low, low or intermediate risk MDS population. These scenarios, for which coverage can be considered, presuming the reasonable and necessary use of ESAs is well documented, are noted below.Epoetin beta is NOT indicated for treatment of anemia in MDS.ESA use for symptomatic anemia in MDS can be considered for the following categories:Patients with MDS with very low, low risk (score<3) per the Revised International Prognostic Scoring System (IPSS-R), orPatients with intermediate risk (IPSS-R score<3.5), orPatients with MDS with low or intermediate- 1 risk (score of 0-1) per the International Prognostic Scoring System (IPSS), orPatients with very low, low or intermediate risk (score of 0-2) per the WHO Prognostic Scoring System (WPSS)ANDWithout del(5q) and serum EPO<500 mU/mL, orWith del(5q) and no chromosome 7 associated abnormalities, on or before starting Lenalidomide with serum EPO<500 mU/mLRequired Documentation Elements:Symptomatic anemia or transfusion dependence and a Hb < 10 g/dL within 1 week of the initial ESA treatmentThe ESA utilized:Epoetin alfa (J0885) or epoetin alfa-epbx biosimilar (Q5106) or darbepoetin (J0881)Weight in kilogramsMDS diagnostic bone marrow biopsy with cytogenetic analysisDocumented evaluation for other anemia contributing factors such as blood loss, hemolysis, renal failure, medications, nutritional deficiencies, thyroid dysfunction, autoimmune disorders and anemia of chronic diseaseEvaluation and treatment of other causes of anemia must occur pre-ESA initiation and at any time thereafter as needed for lack of responsiveness.Iron store results pre-ESA use: serum iron/TIBC (TSAT) and ferritin and at least every 3 months during treatmentTransferrin saturation should be at least 20%, and ferritin should be at least 100 ng/mL to start or continue ESA without correction of iron deficiency.Serum EPO result<500 mU/mLDocumented IPSS-R result of 3 or less for very low, low risk MDS or documented IPSS-R result of 3.5 or less for an intermediate risk MDS or IPSS score of 0-1 or WPSS score of 0-2.Narrative regarding ongoing response to therapyIf the initial dose of an ESA was administered in another setting (i.e., hospital, in a state outside our jurisdiction, or in another facility); subsequent office-administered ESAs must still meet all the above-mentioned requirements. This may require review of outside medical records and confirmation that needed pre-treatment lab results and evaluation were completed appropriately.For patients with symptomatic anemia due to low-risk categories of MDS (Very low, Low or intermediate risk IPPS-R score < 3.5), 1 of the following diagnosis codes should be present on the claim; D46.0, D46.1, D46.20, D46.21, D46.22, D46.A, D46.B, D46.C or D46.Z. In the rare case of essential thrombocythemia progressing to refractory anemia due to secondary myelofibrosis, the dual diagnoses of D47.3 and D75.81 should be reported. Waldenstrom macroglobulinemia cases complicated by neoplastic bone marrow infiltration resulting in symptomatic anemia should simply be reported with C88.0.Inclusion of any other ICD-10 diagnoses on the claim which are non-covered with an EC modifier per NCD 110.21, will preclude payment for the ESA. A JA or JB modifier is required.ESA use for 6-12 weeks would be expected as would RBC transfusion use for symptom management while awaiting an erythroid response.The ESA regimen should be adjusted to maintain the lowest level of Hb/HCT that is sufficient to avoid RBC transfusions. If the rise of Hb is adequate to avoid transfusions or increases > 1 g/dL in any given 2-week period, the dose of epoetin alfa should be reduced by 25% or the dose of darbepoetin alfa can be reduced by 40%. Less frequent dosing would also be an acceptable alternative.If the response is not adequate after 4 weeks, dose escalation, an increase in dose frequency or addition of a myeloid growth factor would be acceptable.ESAs should not be continued for more than 12 weeks if no response is observed.Before beginning ESA therapy, risk of thrombosis should be considered. Hypertension must be controlled.Much higher doses of ESAs are utilized as compared to all the uses noted otherwise in this article. Dosing for epoetin alfa/epoetin alfa-epbx often is in a range of 40,000-60,000 units SQ 1-2 times per week and darbepoetin alfa often in a range of 150-300 mcg SQ every other week.There is currently no consensus regarding an optimal dose/schedule for ESA administration. This decision is left to the treating oncologist.Prophylactic Allogeneic Transfusion Reduction Intent in Presurgical AnemiaDarbepoetin alfa and epoetin beta are NOT indicated for this condition.Forepoetin alfa/epoetin alfa-epbx biosimilar in anemia ina presurgical setting: