VELCADE, Bortezomib Form

Bortezomib (Velcade®) is a proteasome inhibitor. FDA Approved Indication(s) Velcade is indicated for treatment of adult patients with:
• Multiple myeloma (MM) • Mantle cell lymphoma (MCL) 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 bortezomib is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Multiple Myeloma and Mantle Cell Lymphoma (must meet all):

1. Diagnosis of one of the following (a or b): a. MM; b. MCL (B-cell lymphoma subtype);
2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. For Velcade requests, member must use bortezomib, if available, unless contraindicated or clinically significant adverse effects are experienced;
3. Request meets one of the following (a or b): a. Dose does not exceed 1.3 mg/m2; b. 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:
   Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer B. NCCN Recommended Uses (off-label) (must meet all):

4. Diagnosis of one of the following (a-h): a. AIDS-related Kaposi sarcoma (advanced cutaneous, oral, visceral, or nodal disease) - after ≥ 2 prior lines of systemic therapy; Page 1 of 7

   CLINICAL POLICY Bortezomib b. Multicentric Castleman’s disease (B-cell lymphoma subtype) - as subsequent therapy; c. Systemic light chain amyloidosis; d. Adult T-cell leukemia/lymphoma - as subsequent therapy; e. Waldenström macroglobulinemia/lymphoplasmacytic lymphoma; f. T-cell acute lymphoblastic leukemia (T-ALL) – for relapsed or refractory disease; g. Pediatric acute lymphoblastic leukemia (ALL) - as subsequent therapy; h. Pediatric Hodgkin lymphoma (HL) - as subsequent therapy in combination with ifosafamide and vinorelbine;

5. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years (all indications except pediatric ALL and HL);
   4. For Velcade requests, member must use bortezomib, if available, unless contraindicated or clinically significant adverse effects are experienced;
6. 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: Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer C. Other diagnoses/indications (must meet 1 or 2):
7. 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
8. 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.
   II. Continued Therapy A. All Indications in Section I (must meet all):

9. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving the requested agent for a covered indication and has received this medication for at least 30 days;

   2. Member is responding positively to therapy; Page 2 of 7

   CLINICAL POLICY Bortezomib

10. For Velcade requests, member must use bortezomib, if available, unless contraindicated or clinically significant adverse effects are experienced;
    4. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 1.3 mg/m2; b. New 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:
       Medicaid/HIM – 12 months Commercial – 12 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):
11. 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

12. 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, and CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ALL: acute lymphoblastic leukemia FDA: Food and Drug Administration HL: Hodgkin lymphoma MCL: mantle cell lymphoma Appendix B: Therapeutic Alternatives
    Not applicable MM: multiple myeloma
    NCCN: National Comprehensive Cancer Network T-ALL: T-cell acute lymphoblastic leukemia Page 3 of 7

    CLINICAL POLICY Bortezomib Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
    o Patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol, including anaphylactic reactions o Contraindicated for intrathecal administration • Boxed warning(s): none reported V. Dosage and Administration
    Indication Dosing Regimen MM • First-line therapy: 1.3 mg/m2 as a 3 to 5 second bolus IV injection or SC injection in combination with PO melphalan and PO prednisone for nine 6-week treatment cycles.
    • Relapse: 1.3 mg/m2 as a 3 to 5 second bolus IV injection or SC injection as a single agent or in combination with dexamethasone for up to eight 3-week cycles. For therapy beyond eight cycles, see PI for additional dosing options. If relapse occurs ≥ 6 months after a previous response to Velcade, treatment may be restarted at the last tolerated dose. Maximum Dose 1.3 mg/m2
    MCL • First-line therapy: 1.3 mg/m2 as a 3 to 5 second bolus IV 1.3 mg/m2
    injection or SC injection in combination with IV rituximab, cyclophosphamide, doxorubicin and PO prednisone (VcR- CAP) for up to six 3-week treatment cycles, plus two additional cycles if a positive response.
    • Relapse: 1.3 mg/m2 as a 3 to 5 second bolus IV injection or SC injection for up to eight 3-week treatment cycles. Therapy may extend beyond eight cycles. VI. Product Availability
    Single-dose vials for injection:
    • Sterile lyophilized powder for reconstitution: 1 mg, 2.5 mg, 3.5 mg
    • Solution: 3.5 mg/3.5 mL, 3.5 mg/1.4 mL The branded product, Velcade, is only available as 3.5 mg sterile lyophilized powder VII.