POMALYST, Pomalidomide Form

Pomalidomide (Pomalyst®) is a thalidomide analogue. FDA Approved Indication(s) Pomalyst is indicated for the treatment of adult patients: • In combination with dexamethasone, for patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy • With acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART) or in patients with KS who are human immunodeficiency virus (HIV)-negativeThis indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 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 Pomalyst 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. Failure of an immunomodulatory agent (e.g., Revlimid®, Thalomid®) and a proteasome inhibitor (e.g., bortezomib, Kyprolis®, Ninlaro®), unless clinically significant adverse effects are experienced or all are contraindicated;Prior authorization may be required for immunomodulatory agents and proteasome inhibitors.
   5. Prescribed in combination with dexamethasone, unless contraindicated or clinically significant adverse effects are experienced;
2. For Pomalyst requests, member must use pomalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;

3. Pomalyst is not prescribed concurrently with Revlimid or Thalomid; Page 1 of 10

   CLINICAL POLICY Pomalidomide

4. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii) on days 1-21 of repeated 28- day cycles: i. 4 mg per day;
   ii. 1 capsule per day; 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. Kaposi Sarcoma (must meet all):
5. Diagnosis of KS;
   2. Prescribed by or in consultation with an oncologist, dermatologist, immunologist, or infectious disease specialist;
6. Age ≥ 18 years;
   4. If disease is AIDS-related, Pomalyst is prescribed in combination with antiretroviral therapy;
7. Failure of liposomal doxorubicin and paclitaxel, unless clinically significant adverse effects are experienced or both are contraindicated;
8. For Pomalyst requests, member must use pomalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;
9. Pomalyst is not prescribed concurrently with Revlimid or Thalomid;
   8. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii) on days 1-21 of repeated 28- day cycles: i. 5 mg per day;
      ii. 2 capsules per day; 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 C. Systemic Light Chain Amyloidosis (off-label) (must meet all):
10. Diagnosis of systemic light chain amyloidosis;
    2. Prescribed by or in consultation with an oncologist or hematologist;
    3. Age ≥ 18 years;
    4. Disease is relapsed or refractory to prior therapy;
    5. Prescribed in combination with dexamethasone;
    6. For Pomalyst requests, member must use pomalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;

11. Pomalyst is not prescribed concurrently with Revlimid or Thalomid; Page 2 of 10

    CLINICAL POLICY Pomalidomide

12. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii) on days 1-21 of repeated 28- day cycles: i. 4 mg per day;
    ii. 1 capsule per day;
    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 D. Primary Central Nervous System (CNS) Lymphoma (off-label) (must meet all):
13. Diagnosis of primary CNS lymphoma;
    2. Prescribed by or in consultation with an oncologist or hematologist;
    3. Age ≥ 18 years;
    4. Prescribed as a single agent;
    5. Request is for one of the following (a or b): a. Disease is relapsed or refractory to prior therapy; b. Induction therapy if member is unsuitable for or intolerant to high-dose methotrexate;
14. For Pomalyst requests, member must use pomalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;
15. Pomalyst is not prescribed concurrently with Revlimid or Thalomid;
    8. 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 E. Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Protein, Skin Changes (POEMS) Syndrome (off-label) (must meet all):
    9. Diagnosis of POEMS syndrome;
    10. Prescribed by or in consultation with an oncologist or hematologist;
    11. Age ≥ 18 years;
    12. Prescribed in combination with dexamethasone, unless contraindicated or clinically significant adverse effects are experienced;
    13. Prescribed for one of the following (a or b):
        a. Induction therapy for transplant eligible members;
        b. Transplant ineligible members;
16. For Pomalyst requests, member must use pomalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;

17. Pomalyst is not prescribed concurrently with Revlimid or Thalomid; Page 3 of 10

    CLINICAL POLICY Pomalidomide

18. 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 F. Other diagnoses/indications (must meet 1 or 2):
19. 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
20. 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 (meets all):
21. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Pomalyst for a covered indication and has received this medication for at least 30 days;
22. Member is responding positively to therapy;
    3. For Pomalyst requests, member must use pomalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;

23. Pomalyst is not prescribed concurrently with Revlimid or Thalomid;

    5. If request is for a dose increase, request meets one of the following (a, b, or c): a. For KS only: New dose does not exceed both of the following (i and ii) on days 1- 21 of repeated 28-day cycles: i. 5 mg per day;
       ii. 2 capsules per day;
       b. New dose does not exceed both of the following (i and ii) on days 1-21 of repeated 28-day cycles: i. 4 mg per day;
       ii. 1 capsule per day;
       c. 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 Page 4 of 10

    CLINICAL POLICY Pomalidomide 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):

24. 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

25. 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 AIDS: acquired immunodeficiency syndrome CNS: central nervous system FDA: Food and Drug Administration HAART: highly active antiretroviral therapy HIV: human immunodeficiency virus KS: Kaposi sarcoma MM: multiple myeloma POEMS (Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes syndrome) 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 Dose Limit/ Maximum Dose 25 mg/day Revlimid® (lenalidomide) MM Page 5 of 10

    CLINICAL POLICY Pomalidomide Drug Name Dosing Regimen Thalomid® (thalidomide) MM 25 mg PO QD days 1-21 of repeated 28-day cycles. bortezomib (Velcade®) Kyprolis® (carfilzomib) Ninlaro® (ixazomib) First- and second-line therapies: • liposomal doxorubicin (Doxil, Lipodox 50) • paclitaxel Drugs central to first-line therapy regimens: • bortezomib (Velcade®) • Revlimid® (lenalidomide) • melphalan (Alkeran®) Methotrexate (high-dose) 200 mg PO QD.
    MM 1.3 mg/m2/dose for 9 multi-dose treatment cycles with retreatment if indicated.
    MM • Varies MM 4 mg PO once weekly on days 1, 8, 15 of a 28-day treatment cycle KS • Liposomal doxorubicin: 20 mg/m2 IV every 2-3 weeks with a cumulative lifetime dose of 400-450 mg/m2 due to cardiotoxicity • Paclitaxel: 135 mg/m2 IV every 3 weeks or 100 mg/m2 every 2 weeks Systemic Light Chain Amyloidosis • Varies Primary CNS Lymphoma • 8 g/m2 combined with rituximab or rituximab + temozolomide • 3.5 g/m2 combined with vincristine + procarbazine + rituximab or temozolomide

    • rituximab Dose Limit/ Maximum Dose 200 mg/day 1.3 mg/m2/dose Varies
      4 mg/day Varies Varies Varies 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): pregnancy, hypersensitivity • Boxed warning(s): embryo-fetal toxicity; venous and arterial thromboembolism Appendix D: General Information • The NCCN recommends Pomalyst as a preferred 4th line therapy for AIDS-related KS, following HAART, liposomal doxorubicin, and paclitaxel. In Pomalyst’s pivotal KS trial, 61% (11/18) of HIV-positive patients received prior chemotherapy. Page 6 of 10

    CLINICAL POLICY Pomalidomide V. Dosage and Administration
    Indication Dosing Regimen MM
    KS 4 mg PO QD on days 1-21 of repeated 28-day cycles
    5 mg PO QD on days 1-21 of repeated 28-day cycles
    Maximum Dose 4 mg/day
    5 mg/day
    Continue HAART as HIV treatment in patients with AIDS-related KS NCCN KS guidelines (version 1.2022): The NCCN recommends either 4 or 5 mg/day. Although the clinical trial used a dose of 5 mg/day, the NCCN Panel believes that 4 mg is a sufficient dose. VI. Product Availability
    Capsules: 1 mg, 2 mg, 3 mg, 4 mg VII.