TARGRETIN, Bexarotene Form

Bexarotene (Targretin®) is a retinoid X receptor activator.
FDA Approved Indication(s) Targretin capsules are indicated for the treatment of cutaneous manifestations of cutaneous T- cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy. Targretin gel is indicated for the topical treatment of cutaneous lesions in patients with CTCL (Stage IA and IB) who have refractory or persistent disease after other therapies or who have not tolerated other therapies. 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 Targretin is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Cutaneous T-Cell Lymphoma (must meet all):

1. Request is for bexarotene capsules;
   2. Diagnosis of CTCL (see Appendix D for CTCL subtypes);
   3. Prescribed by or in consultation with an oncologist;
   4. Age ≥ 18 years;
   5. For Targretin capsule requests, member must use generic bexarotene capsules, unless contraindicated or clinically significant adverse effects are experienced;
2. Request meets one of the following (a or b): a. Dose does not exceed 400 mg/m2 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. Primary Cutaneous Lymphomas of the Skin (must meet all):

3. Request is for Targretin gel; Page 1 of 7

   CLINICAL POLICY Bexarotene

4. Diagnosis of CTCL or cutaneous B-cell lymphoma (CBCL) (see Appendix D for CTCL and CBCL subtypes);
5. Prescribed by or in consultation with an oncologist;
   4. Age ≥ 18 years;
   5. Disease manifestation is localized to skin only;
   6. Request meets one of the following (a of b): a. Dose does not exceed application of four times 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. 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 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 Targretin for a covered indication, and has received this medication for at least 30 days;
9. Member is responding positively to therapy;
   3. For Targretin capsule requests, member must use generic bexarotene capsules, unless contraindicated or clinically significant adverse effects are experienced;

10. If request is for a dose increase, request meets one of the following (a, b, or c): a. Bexarotene capsules: New dose does not exceed 400 mg/m2 per day; b. Bexarotene gel: New dose does not exceed application of four times 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 Approval duration:
    Page 2 of 7

    CLINICAL POLICY Bexarotene Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less 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 ALCL: anaplastic large cell lymphoma
    ATLL: adult T-cell leukemia/lymphoma C-ALCL: primary cutaneous anaplastic large cell lymphoma CBCL: cutaneous B-cell lymphoma CTCL: cutaneous T-cell lymphoma EBV: Epstein-Barr virus Appendix B: Therapeutic Alternatives
    Not applicable FDA: Food and Drug Administration LyP: lymphomatoid papulosis MF: mycosis fungoides NK cells: natural killer cells RAR: retinoid acid receptor RXR: retinoic X receptors
    Appendix C: Contraindications/Boxed Warnings • Contraindication(s): Pregnancy; known hypersensitivity to bexarotene • Boxed warning(s): Birth defects Page 3 of 7

    CLINICAL POLICY Bexarotene Appendix D: WHO-EORTC Classification of Primary Cutaneous Lymphomas
    • CTCL o Mycosis fungoides (MF) o MF variants and subtypes • Folliculotropic MF • Pagetoid reticulosis • Granulomatous slack skin
    o Sezary syndrome
    o Adult T-cell leukemia/lymphoma (ATLL) o Primary cutaneous CD30+ lymphoproliferative disorders • Primary cutaneous anaplastic large cell lymphoma (C-ALCL) • Lymphomatoid papulosis (LyP) o Subcutaneous panniculitis-like T-cell lymphoma o Extranodal NK/T-cell lymphoma, nasal type o Chronic active EBV infection o Primary cutaneous peripheral T-cell lymphoma, not otherwise specified o Primary cutaneous peripheral T-cell lymphoma, rare subtypes
    • Primary cutaneous gamma/delta T-cell lymphoma • Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma (provisional) • Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (provisional) • Primary cutaneous acral CD8+ T-cell lymphoma (provisional) • CBCL o primary cutaneous marginal zone lymphoma o primary cutaneous follicle center lymphoma o primary cutaneous large B-cell lymphoma, leg type o Epstein-Barr virus mucocutaneous ulcer (provisional) o Intravascular large B-cell lymphoma ___ Extranodal NK-cell lymphoma is considered a CTCL subtype under the policy criteria. V. Dosage and Administration
    Indication Dosing Regimen Oral CTCL 300-400 mg/m2/day PO Topical Initially applied once every other day for the first week. The application frequency should be increased at weekly intervals to once daily, then twice daily, then three times daily and finally four times daily according to individual lesion tolerance Maximum Dose Oral 400 mg/m2/day Topical Four times daily Page 4 of 7

    CLINICAL POLICY Bexarotene VI. Product Availability
    Drug Name Bexarotene capsules (Targretin) Bexarotene 1% gel (Targretin) Availability Capsule: 75 mg Gel: 600 mg active bexarotene per 600 g VII.