THALOMID, Thalidomide Form

Thalidomide (Thalomid®) is an immunomodulatory agent. FDA Approved Indication(s) Thalomid is indicated: • For the treatment of patients with newly diagnosed multiple myeloma (MM) in combination with dexamethasone
• For the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL) • As maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence Limitation(s) of use: Thalomid is not indicated as monotherapy for such ENL treatment in the presence of moderate to severe neuritis. 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 Thalomid 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 ≥ 12 years;
   4. Prescribed in combination with dexamethasone;
   5. Thalomid is not prescribed concurrently with Revlimid® or Pomalyst®;
   6. For Thalomid requests, member must use generic thalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;

2. Request meets one of the following (a or b):* a. Dose does not exceed both of the following (i and ii):
   i. 200 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). Page 1 of 9

   CLINICAL POLICY Thalidomide *Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: 6 months B. Erythema Nodosum Leprosum (must meet all):

3. Diagnosis of ENL;
   2. Prescribed by or in consultation with an infectious disease specialist, immunologist, or dermatologist;
4. Age ≥ 12 years;
   4. Thalomid is not prescribed concurrently with Revlimid or Pomalyst;
   5. For Thalomid requests, member must use generic thalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;
5. Dose does not exceed both of the following (a and b):
   a. 400 mg per day; b. 2 capsules per day. Approval duration: 6 months C. Myeloproliferative Neoplasms (off-label) (must meet all):
6. Diagnosis of myeloproliferative neoplasms (myelofibrosis) with associated anemia;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 12 years;
   4. Member meets one of the following (a or b): a. Serum EPO ≥ 500 mU/mL; b. Serum EPO < 500 mU/mL, and no response or loss of response to erythropoietic stimulating agents (ESA; Retacrit® is preferred); Prior authorization may be required
7. Prescribed in combination with prednisone;
   
   6. Thalomid is not prescribed concurrently with Revlimid or Pomalyst;
   7. For Thalomid requests, member must use generic thalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;
8. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii):
   i. 400 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: 6 months D. Castleman’s Disease (off-label) (must meet all):

9. Diagnosis of multicentric Castleman’s disease (MCD);

   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 12 years;
   4. Request is for one of the following (a or b): a. Active idiopathic MCD without organ failure, and all of the following (i, ii, and iii): i. Human immunodeficiency virus (HIV) negative; ii. Human herpesvirus-8 (HHV-8) negative; Page 2 of 9

   CLINICAL POLICY Thalidomide iii. Prescribed in combination with cyclophosphamide and prednisone; b. As subsequent therapy for disease that has progressed following treatment of relapsed/refractory or progressive disease (see Appendix E);

10. Thalomid is not prescribed concurrently with Revlimid or Pomalyst;
    6. For Thalomid requests, member must use generic thalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;
11. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii):
    i. 400 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: 6 months E. Kaposi Sarcoma (off-label) (must meet all):
12. Diagnosis of Kaposi sarcoma;
    2. Prescribed by or in consultation with an oncologist or immunologist;
    3. Age ≥ 12 years;
    4. If AIDS-related, Thalomid is prescribed in combination with antiretroviral therapy;
    5. Member has corticosteroid-refractory immune reconstitution inflammatory syndrome;
    6. Failure of liposomal doxorubicin and paclitaxel, unless clinically significant adverse effects are experienced or both are contraindicated;
13. Thalomid is not prescribed concurrently with Revlimid or Pomalyst;
    8. For Thalomid requests, member must use generic thalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;
14. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii):
    i. 400 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: 6 months F. Histiocytic Neoplasms (off-label) (must meet all):
15. Diagnosis of Langerhans cell histiocytosis or Rosai-Dorfman disease;
    2. Prescribed by or in consultation with an oncologist or hematologist;
    3. Age ≥ 12 years;
    4. Request is for use as single-agent therapy;
    5. Thalomid is not prescribed concurrently with Revlimid or Pomalyst;
    6. For Thalomid requests, member must use generic thalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;

16. Request meets one of the following (a or b):* a. Dose does not exceed both of the following (i and ii):
    i. 400 mg per day; ii. 2 capsules per day; Page 3 of 9

    CLINICAL POLICY Thalidomide 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: 6 months G. Aphthous Stomatitis or Ulcers (off-label) (must meet all):

17. Diagnosis of HIV-associated aphthous ulcers or aphthous stomatitis in immunocompetent members;
18. Age ≥ 12 years;
    3. Failure of a systemic corticosteroid, unless clinically significant adverse effects are experienced or all are contraindicated;
19. Thalomid is not prescribed concurrently with Revlimid or Pomalyst;
    5. For Thalomid requests, member must use generic thalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;
20. Request meets one of the following (a or b):* a. Dose does not exceed both of the following (i and ii):
    i. 400 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). Approval duration: 6 months H. Other diagnoses/indications (must meet 1 or 2):
21. 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
22. 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):
23. Currently receiving medication via Centene benefit or documentation supports that member is currently receiving Thalomid for a covered indication and has received this medication for at least 30 days;

24. Member is responding positively to therapy;
    Page 4 of 9

    CLINICAL POLICY Thalidomide

25. Thalomid is not prescribed concurrently with Revlimid or Pomalyst;
    4. For Thalomid requests, member must use generic thalidomide, if available, unless contraindicated or clinically significant adverse effects are experienced;
    5. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed one of the following (i or ii):
       i. For MM (a and b): a) 200 mg per day;
       b) 1 capsule per day
       ii. For all other indications (a and b):
       a) 400 mg per day; b) 2 capsules per day;
       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: 12 months B. Other diagnoses/indications (must meet 1 or 2):
26. 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

27. 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 ENL: erythema nodosum leprosum FDA: Food and Drug Administration
    MCD: multicentric Castleman’s disease MM: multiple myeloma EPO: erythropoietin NCCN: National Comprehensive Cancer Network Page 5 of 9

    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.
    Dosing Regimen Drug Name Dose Limit/ Maximum Dose 20 mg/m2/dose liposomal doxorubicin (Doxil®, Lipodox® 50) paclitaxel Kaposi sarcoma: 20 mg/m2 IV every 2-3 weeks with a cumulative lifetime dose of 400-450 mg/m2 due to cardiotoxicity Kaposi sarcoma: 135 mg/m2 IV every 3 weeks or 100 mg/m2 IV every 2 weeks 20 to 40 mg PO QD for four to seven days See regimen prednisone 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. See regimen Appendix C: Contraindications/Boxed Warnings • Contraindication(s): pregnancy; hypersensitivity • Boxed warning(s): embryo-fetal toxicity and venous thromboembolism Appendix D: General Information
    • Thalomid is only available under a restricted distribution program called the Thalomid REMS program due to a black box warning for embryo-fetal toxicity. Patient and physician enrollment in the manufacturer's REMS program is required. Appendix E: Initial Treatment for Relapsed or Progressive MCD per NCCN • Single-agent therapies of etoposide, vinblastine, liposomal doxorubicin; or • Combination therapy of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) ± rituximab, CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) ± rituximab, CVP (cyclophosphamide, vincristine, and prednisone) ± rituximab, or liposomal doxorubicin ± rituximab V. Dosage and Administration
    Indication MM ENL Dosing Regimen 200 mg PO QD 100 to 300 mg PO QD Maximum Dose 200 mg/day 400 mg/day VI. Product Availability
    Capsules: 50 mg, 100 mg, 150 mg, 200 mg VII.