LEUKINE, Sargramostim Form

Sargramostim (Leukine®) is a recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF). FDA Approved Indication(s) Leukine is indicated: • To shorten time to neutrophil recovery and to reduce the incidence of severe and life- threatening infections and infections resulting in death following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia (AML); • For the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis and autologous transplantation in adult patients; • For the acceleration of myeloid reconstitution following autologous peripheral blood progenitor cell (PBPC) or bone marrow transplantation in adult and pediatric patients 2 years of age and older with non-Hodgkin's lymphoma (NHL), acute lymphoblastic leukemia (ALL) and Hodgkin's lymphoma (HL); • For the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older;
• For treatment of delayed neutrophil recovery or graft failure after autologous or allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older; • To increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [H-ARS]). Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Leukine is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acute Myelogenous Leukemia (must meet all):

1. Diagnosis of AML;

   2. Prescribed for use following induction therapy for AML;
   3. Age ≥ 55 years;
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   CLINICAL POLICY Sargramostim

2. Member meets one of the following (a or b): a. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E); b. Failure of Zarxio® unless contraindicated or clinically significant adverse effects are experienced;
   *Prior authorization may be required for Zarxio
3. Leukine will not be prescribed concurrently with other colony stimulating factors (e.g., filgrastim, pegfilgrastim) within any chemotherapy cycle;
4. Dose does not exceed 250 mcg/m2 IV daily. Approval duration:
   Medicaid/HIM – 6 months
   Commercial - 6 months or to the member’s renewal date, whichever is longer B. Peripheral Blood Progenitor Cell Collection and Transplantation (must meet all):
5. Prescribed for one of the following (a or b): a. Mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis and autologous transplantation; b. Following autologous PBPC transplantation in members with NHL, ALL, HL for acceleration of myeloid reconstitution;
6. Age ≥ 2 years;
   
   3. Member meets one of the following (a or b): a. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E); b. Failure of Zarxio® unless contraindicated or clinically significant adverse effects are experienced;
      *Prior authorization may be required for Zarxio
7. Leukine will not be prescribed concurrently with other colony stimulating factors (e.g., filgrastim, pegfilgrastim) within any chemotherapy cycle;
8. Dose does not exceed 250 mcg/m2 IV or SC daily. Approval duration:
   Medicaid/HIM – 6 months
   Commercial - 6 months or to the member’s renewal date, whichever is longer C. Bone Marrow Transplantation (must meet all):
9. Prescribed for use in one of the following settings (a, b, or c): a. Following autologous BMT in members with NHL, ALL, or HL for acceleration of myeloid reconstitution;
   b. Following allogeneic BMT for acceleration of myeloid reconstitution; c. Following BMT where engraftment is delayed or has failed;
10. Age ≥ 2 years;
    
    3. Leukine will not be prescribed concurrently with other colony stimulating factors (e.g., filgrastim, pegfilgrastim) within any chemotherapy cycle;

11. Member meets one of the following (a or b): a. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E); b. Failure of Zarxio® unless contraindicated or clinically significant adverse effects are experienced;
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    CLINICAL POLICY Sargramostim *Prior authorization may be required for Zarxio

    5. Dose does not exceed 500 mcg/m2 IV daily. Approval duration:
       Medicaid/HIM – 6 months
       Commercial - 6 months or to the member’s renewal date, whichever is longer D. Acute Radiation Syndrome (must meet all):
12. Prescribed for use following suspected or confirmed acute exposure to myelosuppressive doses of radiation;
13. Member meets one of the following (a or b): a. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E); b. Failure of Zarxio® unless contraindicated or clinically significant adverse effects are experienced;
    *Prior authorization may be required for Zarxio
14. Leukine will not be prescribed concurrently with other colony stimulating factors (e.g., filgrastim, pegfilgrastim) within any chemotherapy cycle;
15. Dose does not exceed one of the following (a, b, or c):
    a. Weight <15 kg: 12 mcg/kg SC daily; b. Weight 15 kg to 40 kg: 10 mcg/kg SC daily; c. Weight > 40 kg: 7 mcg/kg SC daily. Approval duration:
    Medicaid/HIM – 6 months
    Commercial - 6 months or to the member’s renewal date, whichever is longer E. Other diagnoses/indications (must meet all):
16. Member meets one of the following (a or b): a. Member must use Zarxio, unless both are contraindicated or clinically significant adverse effects are experienced;Prior authorization may be required for Zarxio b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E);

17. Must meet one of the following (a or b): a. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (i or ii): i. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or ii. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or b. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy Page 3 of 9

    CLINICAL POLICY Sargramostim for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    II. Continued Therapy A. All Indications in Section I (must meet all):

18. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
    2. Member is responding positively to therapy;
    3. Leukine will not be prescribed concurrently with other colony stimulating factors (e.g., filgrastim, pegfilgrastim) within any chemotherapy cycle;
19. Dose does not exceed the FDA-approved maximum recommended dose for the relevant indication in Section V. Approval duration:
    Medicaid/HIM – 6 months
    Commercial - 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet all):
20. Member meets one of the following (a or b): a. Member must use Zarxio, unless both are contraindicated or clinically significant adverse effects are experienced;Prior authorization may be required for Zarxio b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E);

21. Must meet one of the following (a or b): a. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (i or ii): i. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or ii. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or b. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
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    CLINICAL POLICY Sargramostim III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ALL: acute lymphoblastic leukemia AML: acute myelogenous leukemia BMT: bone marrow transplantation FDA: Food and Drug Administration GM-CSF: granulocyte-macrophage colony stimulating factor H-ARS: hematopoietic syndrome of acute radiation syndrome NHL: non-Hodgkin's lymphoma PBPC: peripheral blood progenitor cell
    Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent and may require prior authorization.
    Drug Dosing Regimen Dose Limit/
    Maximum Dose AML: 30 mcg/kg/day [IV] or 24 mcg/kg/day [SC]
    Zarxio (filgrastim-sndz), AML: 5 mcg/kg SC or IV QD BMT: 10 mcg/kg IV or SC infusion QD PBPC collection: 10 mcg/kg SC bolus or continuous infusion QD Acute Radiation Syndrome: 10 mcg/kg SC QD BMT, PBPC collection, Acute Radiation Syndrome: 10 mcg/kg/day Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): history of serious allergic reactions, including anaphylaxis • Boxed warning(s): none reported Appendix D: General Information • Because of potential sensitivity of rapidly dividing hematopoietic progenitor cells, Leukine should not be administered simultaneously with cytotoxic chemotherapy or radiotherapy or within 24 hours preceding or following chemotherapy or radiotherapy. • Use Leukine with caution in patients with pre-existing fluid retention, pulmonary infiltrates, or congestive heart failure. Page 5 of 9

    CLINICAL POLICY Sargramostim Appendix E: States with Regulations against Redirections in Cancer State Step Therapy Prohibited? Yes Yes FL GA IA LA NV OH PA TN TX Yes Yes Yes Yes Yes Yes Yes Notes For stage 4 metastatic cancer and associated conditions. For stage 4 metastatic cancer. Redirection does not refer to review of medical necessity or clinical appropriateness. For standard of care stage 4 cancer drug use, supported by peer- reviewed, evidence-based literature, and approved by FDA. For stage 4 advanced, metastatic cancer or associated conditions. Exception if “clinically equivalent therapy, contains identical active ingredient(s), and proven to have same efficacy. Stage 3 and stage 4 cancer patients for a prescription drug to treat
    the cancer or any symptom thereof of the covered person Applies to Commercial and HIM requests only For stage 4 metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer and associated conditions V. Dosage and Administration
    Indication AML PBPC collection and transplantation Myeloid reconstitution after autologous or allogeneic BMT BMT failure or engraftment delay Acute Radiation Syndrome Dosing Regimen 250 mcg/m2/day IV over a 4 hour period approximately on day 11 or four days following the completion of induction chemotherapy 250 mcg/m2/day administered IV over 24 hours or SC once daily 250 mcg/m2/day IV over a 2 hour period beginning two to four hours after bone marrow infusion, and not less than 24 hours after the last dose of chemotherapy or radiotherapy 250 mcg/m2/day for 14 days as a 2 hour IV infusion Weight-based dose SC QD:

    40 kg: 7 mcg/kg 15 to 40 kg: 10 mcg/kg <15 kg: 12 mcg/kg VI. Product Availability
    Lyophilized powder: 250 mcg single-dose vial Solution: 500 mcg/mL multiple-dose vial Maximum Dose 250 mcg/m2 IV daily 250 mcg/m2 IV or SC daily 500 mcg/m2 IV daily 500 mcg/m2 IV daily See dosing regimen Page 6 of 9

    CLINICAL POLICY Sargramostim VII.