ISTODAX (OVERFILL), Romidepsin Form

Romidepsin (Istodax®) is a histone deacetylase inhibitor. FDA Approved Indication(s) Istodax is indicated for the treatment of cutaneous T-cell lymphoma (CTCL) in adult patients who have received at least one prior systemic therapy. 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 Istodax and romidepsin injection solution are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. T-Cell Lymphoma (must meet all):

1. Diagnosis of one of the following T-cell lymphomas (a, b, c, d, or e): a. CTCL (see Appendix D for examples of subtypes); b. Hepatosplenic T-cell lymphoma; c. Extranodal NK/T-cell lymphoma; d. Peripheral T-cell lymphoma (see Appendix E for examples of subtypes); e. Breast implant-associated anaplastic large cell lymphoma;
2. Prescribed by or in consultation with an oncologist or hematologist;
   
   3. Age ≥ 18 years;
   4. Failure of at least one prior systemic therapy, unless member has mycosis fungoides or Sezary syndrome;
3. For Istodax requests, member must use romidepsin, if available, unless contraindicated or clinically significant adverse effects are experienced;

4. Request meets one of the following (a or b): a. Dose does not exceed 14 mg/m2 on days 1, 8, and 15 of a 28-day cycle; 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 Page 1 of 7

   CLINICAL POLICY Romidepsin B. Other diagnoses/indications (must meet 1 or 2):

5. 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
6. 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. T-Cell Lymphoma (must meet all):
7. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Istodax for a covered indication and has received this medication for at least 30 days;
8. Member is responding positively to therapy;
   3. For Istodax requests, member must use romidepsin, if available, unless contraindicated or clinically significant adverse effects are experienced;
9. If request is for a dose increase, meets one of the following (a or b): a. New dose does not exceed 14 mg/m2 on days 1, 8, and 15 of a 28-day 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: 12 months
   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 Page 2 of 7

    CLINICAL POLICY Romidepsin

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.
    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 CTCL: cutaneous T-cell lymphoma
    FDA: Food and Drug Administration MF: mycosis fungoides Appendix B: Therapeutic Alternatives Not applicable
    Appendix C: Contraindications/Boxed Warnings None reported NCCN: National Comprehensive Cancer Center Appendix D: WHO-EORTC Classification of CTCL* with Primary Cutaneous Manifestations • Mycosis fungoides (MF) o MF variants and subtypes  Folliculotropic MF  Pagetoid reticulosis  Granulomatous slack skin • Sezary syndrome • Adult T-cell leukemia/lymphoma • Primary cutaneous CD30+ lymphoproliferative disorders o Cutaneous anaplastic large cell lymphoma o Lymphomatoid papulosis • Subcutaneous panniculitis-like T-cell lymphoma • Primary cutaneous peripheral T-cell lymphoma, not otherwise unspecified • Primary cutaneous peripheral T-cell lymphoma, rare subtypes
    o Primary cutaneous delta/gamma T-cell lymphoma o CD8+ AECTCL (primary cutaneous aggressive epidermotropic CD8+ cytotoxic T- cell lymphoma) o Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder o Primary cutaneous acral CD8+ T-cell lymphoma • MF is the most common cutaneous T-cell lymphoma. Sezary syndrome is closely related to MF accounting for less than 5% of cutaneous lymphomas. ____ Page 3 of 7

    CLINICAL POLICY Romidepsin CTCL is classified as a non-Hodgkin T-cell lymphoma. CTCL classification schemes are periodically advanced as new information becomes available; therefore, the above list is provided as general guidance. For additional information, see WHO’s 2016 updated classification of hematological malignancies for a complete list of lymphoid neoplasms, including CTCL. Appendix E: Types of Peripheral T-Cell Lymphomas • Peripheral T-cell lymphoma, not otherwise specified • Enteropathy-associated T-cell lymphoma (EATL) • Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL)
    • Angioimmunoblastic T-cell lymphoma (AITL), including nodal peripheral T-cell lymphoma with TFH phenotype (PTCL, TFH), and follicular T-cell lymphoma (FTCL) • Anaplastic large cell lymphoma ____ *Although the FDA-labeled indication for peripheral T-cell lymphoma was withdrawn in August 2021 following findings from the confirmatory phase 3 trial, the NCCN continues to support use in this indication based on the results of the phase 2 trial and other subsequent trials.
    V. Dosage and Administration
    Indication CTCL Dosing Regimen 14 mg/m2 IV over a 4-hour period on days 1, 8, and 15 of a 28-day cycle. Repeat cycles every 28 days provided that the patient continues to benefit from and tolerates the drug. Maximum Dose 14 mg/m2/dose VI. Product Availability
    Single-dose vial: 10 mg VII.