MYLOTARG, Gemtuzumab Ozogamicin Form

Gemtuzumab ozogamicin (Mylotarg™) is a CD33 directed antibody and cytotoxic drug conjugate. FDA Approved Indication(s) Mylotarg is indicated for the treatment of: • Newly-diagnosed CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients 1 month and older • Relapsed or refractory CD33-positive AML in adults and in pediatric patients 2 years and older 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 Mylotarg is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acute Myeloid Leukemia (must meet all):

1. Diagnosis of CD33-positive AML;
2. Prescribed by or in consultation with an oncologist or hematologist;

3. Member meets (a or b): a. Age ≥ 1 month with newly diagnosed disease; b. Age ≥ 2 years with relapsed or refractory disease;

   4. Mylotarg is prescribed as one of the following (a, b, c, or d):
      a. As combination therapy with daunorubicin and cytarabine for newly diagnosed disease: up to 5 doses; b. As single-agent therapy for newly diagnosed disease: up to 10 doses; c. As single-agent therapy for relapsed or refractory disease: up to 3 doses; d. As a component of repeating the initial successful induction regimen for relapsed or refractory disease if ≥ 12 months since induction regimen: up to 3 doses;
   5. Request meets one of the following (a, b, c, d, or e):* a. Age 1 month to < 18 years: Newly diagnosed disease as combination therapy with standard chemotherapy (i and ii): i. Induction - 1 cycle (1 vial): dose does not exceed 0.1 mg/kg (body surface area [BSA] < 0.6 m2) or 3 mg/m2 (BSA ≥ 0.6 m2) given once; Page 1 of 7

   CLINICAL POLICY
   Gemtuzumab Ozogamicin ii. Intensification - 1 cycle (1 vial): dose does not exceed 0.1 mg/kg (BSA < 0.6 m2) or 3 mg/m2 (BSA ≥ 0.6 m2) given once; b. Age ≥ 18 years: Newly diagnosed disease as combination therapy with daunorubicin and cytarabine (i and ii): i. Induction - 1 cycle (3 vials): dose does not exceed 3 mg/m2 on Days 1, 4, and 7; ii. Consolidation - 2 cycles (2 vials): dose does not exceed 3 mg/m2 on Day 1 of each cycle; c. Age ≥ 18 years: Newly diagnosed disease as single-agent therapy (i and ii):
   i. Induction - 1 cycle: dose does not exceed 6 mg/m2 on Day 1, and 3 mg/m2 on Day 8; ii. Continuation therapy - 8 cycles: dose does not exceed 2 mg/m2 on Day 1 of each cycle; d. Age ≥ 2 years: Relapsed or refractory disease (single-agent regimen): single course: dose does not exceed 3 mg/m2 on Days 1, 4, and 7 (3 vials); e. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). *Prescribed regimen must be FDA-approved or recommended by NCCN. Approval duration: 12 months
   B. Acute Promyelocytic Leukemia (off-label) (must meet all):

   1. Diagnosis of acute promyelocytic leukemia;
4. Prescribed by or in consultation with an oncologist or hematologist;
5. Age ≥ 18 years;
6. Mylotarg is prescribed for no more than 10 doses total;

7. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).Prescribed regimen must be FDA-approved or recommended by NCCN.
   Approval duration: 12 months
   C. Other diagnoses/indications (must meet 1 or 2):

   1. 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 (a or b): a. 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 b. 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
   2. 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 Page 2 of 7

   CLINICAL POLICY
   Gemtuzumab Ozogamicin 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.
   II. Continued Therapy A. All Indications in Section I (must meet all):

   1. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Mylotarg for a covered indication and has received this medication for at least 30 days;
   2. Member is responding positively to therapy;
8. For AML, member has NOT received the maximum recommended doses as described below (a, b, c, or d):
   a. As combination therapy with daunorubicin and cytarabine for newly diagnosed disease: up to 5 doses; b. As single-agent therapy for newly diagnosed disease: up to 10 doses; c. As single-agent thearpy for relapsed or refractory disease: up to 3 doses; d. As a component of repeating the initial successful induction regimen for relapsed or refractory disease if ≥ 12 months since induction regimen: up to 3 doses;
   4. For acute promyelocytic leukemia, member has not received ≥ 10 doses;

9. If request is for a dose increase, request meets one of the following (a, b, c, d, or e): a. Age 1 month to < 18 years: Newly diagnosed disease as combination therapy with standard chemotherapy (i and ii): i. Induction - 1 cycle (1 vial): dose does not exceed 0.1 mg/kg (body surface area [BSA] < 0.6 m2) or 3 mg/m2 (BSA ≥ 0.6 m2) given once; ii. Intensification - 1 cycle (1 vial): dose does not exceed 0.1 mg/kg (BSA < 0.6 m2) or 3 mg/m2 (BSA ≥ 0.6 m2) given once; b. Age ≥ 18 years: Newly diagnosed disease as combination therapy with daunorubicin and cytarabine (i and ii): i. Induction - 1 cycle (3 vials): dose does not exceed 3 mg/m2 on Days 1, 4, and 7; ii. Consolidation - 2 cycles (2 vials): dose does not exceed 3 mg/m2 on Day 1 of each cycle; c. Age ≥ 18 years: Newly diagnosed disease as single-agent therapy (i and ii):
   i. Induction - 1 cycle: dose does not exceed 6 mg/m2 on Day 1, and 3 mg/m2 on Day 8; ii. Continuation therapy - 8 cycles: dose does not exceed 2 mg/m2 on Day 1 of each cycle; d. Age ≥ 2 years: Relapsed or refractory disease (single-agent regimen): single course: dose does not exceed 3 mg/m2 on Days 1, 4, and 7 (3 vials); e. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN.
   Approval duration: 12 months Page 3 of 7

   CLINICAL POLICY
   Gemtuzumab Ozogamicin B. Other diagnoses/indications (must meet 1 or 2):

   1. 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 (a or b): a. 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 b. 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
   2. 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.
      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, CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key AML: acute myeloid leukemia
      BSA: body surface area FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives Not applicable NCCN: National Comprehensive Cancer Center Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity to Mylotarg or any of its components • Boxed warning(s): hepatotoxicity V. Dosage and Administration
      Indication AML newly- diagnosed (combination regimen) Dosing Regimen Adults:
      Induction: 3 mg/m2 IV (up to one 4.5 mg vial) on Days 1, 4, and 7 in combination with daunorubicin and cytarabine. If a second induction cycle is required, do NOT administer Mylotarg. Maximum Dose Induction: 4.5 mg/dose (1 cycle) Consolidation: 4.5 mg/dose (2 cycles) Page 4 of 7

   CLINICAL POLICY
   Gemtuzumab Ozogamicin Indication Dosing Regimen Maximum Dose Consolidation: 3 mg/m2 IV on Day 1 (up to one 4.5 mg vial) in combination with daunorubicin and cytarabine for 2 cycles. Pediatric patients ≥ 1 month:
   • BSA ≥ 0.6 m2: 3 mg/m2 IV
   • BSA < 0.6 m2 : 0.1 mg/kg IV Adults: Induction: 6 mg/m2 IV on Day 1 and 3 mg/m2 on Day 8 for 1 cycle Continuation: 2 mg/m2 IV on Day 1 every 4 weeks for up to 8 cycles Age ≥ 2 years: 3 mg/m2 IV (up to one 4.5 mg vial) on Days 1, 4, and 7 for 1 cycle Induction pediatric: 1 cycle
   Consolidation pediatric: 1 cycle Induction: 6 mg/m2/dose (1 cycle) Maintenance: 2 mg/m2/dose every 4 weeks (8 cycles) 4.5 mg/dose (1 cycle) AML newly- diagnosed (single- agent regimen) AML relapsed or refractory (single- agent regimen) VI. Product Availability Single-dose vial: 4.5 mg
   VII.