ZOLINZA, Vorinostat Form

Vorinostat (Zolinza®) is a histone deacetylase (HDAC) inhibitor. FDA Approved Indication(s) Zolinza is indicated for the treatment of cutaneous manifestations in patients with cutaneous T- cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic 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 Zolinza is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Cutaneous T-Cell Lymphoma (must meet all):

1. Diagnosis of CTCL;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. For Zolinza requests; member must use vorinostat, 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 400 mg (4 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 B. Other diagnoses/indications (must meet 1 or 2):

3. 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: Page 1 of 6

   CLINICAL POLICY Vorinostat 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

4. 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. Cutaneous T-Cell Lymphoma (must meet all):
5. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Zolinza for CTCL and has received this medication for at least 30 days;
6. Member is responding positively to therapy;
   3. For Zolinza requests; member must use vorinostat, if available, unless contraindicated or clinically significant adverse effects are experienced;
7. If request is for a dose increase, request meets one of the following (a or b):
   a. New dose does not exceed 400 mg (4 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: Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
8. 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

9. 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 Vorinostat 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 AECTCL: aggressive epidermotropic cutaneous t-cell lymphoma
   ATLL: adult t-cell leukemia/lymphoma
   ALCL: anaplastic large cell lymphoma
   CTCL: cutaneous T-cell lymphoma EBV: epstein-bar virus FDA: Food and Drug Administration HDAC: histone deacetylase Appendix B: Therapeutic Alternatives
   Not applicable MF: mycosis fungoide NCCN: National Comprehensive Cancer Network
   NHL: non-hodgkin’s lymphoma
   NK: natural killer NOS: not otherwise specified SS: sezary syndrome Appendix C: Contraindications/Boxed Warnings None reported Appendix D: World Health Organization-European Organization for Research and Treatment of Cancer, 2018 - Classification of CTCL
   • Mycosis fungoides (MF) o MF variants and subtypes  Folliculotropic MF  Pagetoid reticulosis  Granulomatous slack skin • Sezary syndrome (SS) • Adult T-cell leukemia/lymphoma (ATLL) • Primary cutaneous CD30+ lymphoproliferative disorders o Cutaneous anaplastic large cell lymphoma (ALCL) o Lymphomatoid papulosis • Subcutaneous panniculitis-like T-cell lymphoma • Extranodal natural killer (NK)*/T-cell lymphoma, nasal type • Chronic active Epstien-Bar virus (EBV) infection • Primary cutaneous peripheral T-cell lymphoma, rare subtypes o Primary cutaneous gamma-delta T-cell lymphoma o Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma (CD8+ AECTCL) o Primary cutaneous CD4+ small/medium-sized T-cell lymphoproliferative disorder o Primary cutaneous acral CD8+ T-cell lymphoma • Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (NOS) Page 3 of 6

   CLINICAL POLICY Vorinostat ___ Non-Hodgkin’s lymphomas (NHLs) include lymphoproliferative disorders originating in B-lymphocytes, T- lymphocytes, and natural killer cells. Cutaneous T-cell lymphomas (CTCLs) are a subset of NHLs characterized by skin involvement and the potential to progress to lymph nodes, blood, and visceral organs. Mycosis fungoides, the most common CTCL, is an extranodal NHL of mature T-cells with primary skin involvement. Sezary syndrome, a less common CTCL, is characterized by significant blood involvement and lymphadenopathy. *Extranodal NK-cell lymphoma is considered a CTCL subtype under the policy criteria. V. Dosage and Administration
   Indication CTCL Dosing Regimen 400 mg PO QD Maximum Dose 400 mg/day VI. Product Availability
   Capsule: 100 mg VII.