NINLARO, Ixazomib Citrate Form

Ixazomib (Ninlaro®) is a proteasome inhibitor. FDA Approved Indication(s) Ninlaro is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. Limitations of Use: Ninlaro is not recommended for use in the maintenance setting or in newly diagnosed MM in combination with lenalidomide and dexamethasone outside of controlled clinical trials. 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 Ninlaro is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Multiple Myeloma (must meet all):

1. Diagnosis of MM;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Member has received at least one prior therapy (see Appendix B);
   5. Prescribed in one of the following ways (a or b): a. In combination with dexamethasone with or without either Revlimid® or cyclophosphamide; b. All of the following (i, ii, and iii): In combination with dexamethasone and Pomalyst®; i. ii. Member has received at least two prior therapies including an immunomodulatory agent and a proteasome inhibitor; iii. Member has demonstrated disease progression on or within 60 days of completion of the last therapy; *Prior authorization may be required for Revlimid, Pomalyst, or cyclophosphamide.

2. Request meets one of the following (a or b):*
   a. Dose does not exceed 4 mg (1 tablet) per week for 3 weeks of a 28-day (4-week) treatment cycle; Page 1 of 7

   CLINICAL POLICY Ixazomib 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 – 12 months or duration of request, whichever is less B. Systemic Light Chain Amyloidosis (off-label) (must meet all):

3. Diagnosis of relapsed or refractory systemic light chain amyloidosis;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Prescribed in one of the following ways (a, b, or c): a. As a single agent; b. In combination with dexamethasone; c. In combination with dexamethasone and Revlimid;Prior authorization may be required for Revlimid
4. 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 – 12 months or duration of request, whichever is less C. Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma (off-label) (must meet all):
   1. Diagnosis of Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Prescribed in combination with Rituxan® and dexamethasone; Prior authorization may be required for Rituxan.
5. 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 – 12 months or duration of request, whichever is less D. Other diagnoses/indications (must meet 1 or 2):

6. 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 Page 2 of 7

   CLINICAL POLICY Ixazomib 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

7. 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):
8. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Ninlaro for a covered indication and has received this medication for at least 30 days;
9. Member is responding positively to therapy;
   3. If request is for a dose increase, request meets one of the following (a or b):
      a. New dose does not exceed 4 mg (1 tablet) per week for 3 weeks of a 28-day (4- week) treatment cycle; 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 duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
10. 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

11. 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 Ixazomib 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 FDA: Food and Drug Administration MM: multiple myeloma NCCN: National Comprehensive Cancer Network 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 for all relevant lines of business and may require prior authorization. Drug Name Dosing Regimen Varies Varies Varies Dose Limit/ Maximum Dose Varies Varies Varies Varies Varies Varies Varies bortezomib/Revlimid® (lenalidomide) /dexamethasone bortezomib/cyclophosphamide/dexamethasone bortezomib/doxorubicin (or liposomal doxorubicin)/ dexamethasone Kyprolis® (carfilzomib)/Revlimid® (lenalidomide) /dexamethasone Kyprolis® (carfilzomib)/cyclophosphamide/ dexamethasone bortezomib/dexamethasone bortezomib/Thalomid® (thalidomide)/dexamethasone cyclophosphamide/Revlimid® (lenalidomide)/dexamethasone Revlimid® (lenalidomide)/dexamethasone VTD-PACE (dexamethasone/Thalomid® (thalidomide)/cisplatin/doxorubicin/ cyclophosphamide/etoposide/bortezomib) Revlimid® (lenalidomide)/low-dose dexamethasone Darzalex® (daratumumab) or Darzalex Faspro™ (daratumumab/hyaluronidase-fihj)/bortezomib/melphan/ prednisone Darzalex® (daratumumab) or Darzalex Faspro™ (daratumumab/hyaluronidase-fihj)/Revlimid® (lenalidomide)/ dexamethasone 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. Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Appendix C: Contraindications/Boxed Warnings None reported Page 4 of 7

    CLINICAL POLICY Ixazomib Appendix D: General Information • NCCN includes a category 2B recommendation for use of Ninlaro as maintenance therapy. The prescribing information for Ninlaro states that in two prospective randomized clinical trials in MM in the maintenance setting, treatment with Ninlaro resulted in increased deaths. Treatment of patients with Ninlaro for MM in the maintenance setting is not recommended outside of controlled trials. V. Dosage and Administration
    Indication Dosing Regimen MM 4 mg PO on Days 1, 8, and 15 of a 28-day cycle. See Ninlaro Prescribing Information for Revlimid and dexamethasone dosing. Maximum Dose 4 mg/week for 3 weeks of a 28- day (4-week) treatment cycle VI. Product Availability
    Capsules: 2.3 mg, 3 mg, 4 mg VII.