FOLOTYN, Pralatrexate Form

Pralatrexate injection (Folotyn®) is a folate analog metabolic inhibitor. ____ *For Health Insurance Marketplace (HIM), if request is through pharmacy benefit, Folotyn (40 mg/2mL vial) is non-formulary and cannot be approved using these criteria; refer to the formulary exception policy, HIM.PA.103.
FDA Approved Indication(s) Folotyn is indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).
This 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 Folotyn is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Peripheral T-Cell Lymphoma (must meet all):

1. Diagnosis of PTCL (see Appendix D for examples of PTCL subtypes);
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. One of the following (a or b): a. Prescribed as initial palliative intent therapy; b. Failure of at least one prior therapy (see Appendix B for examples);Prior authorization may be required for prior therapies

2. Prescribed as a single-agent therapy;

   6. Request meets one of the following (a or b): a. Dose does not exceed 30 mg/m2 once weekly for 6 weeks in 7-week cycles; 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 – 6 months
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   CLINICAL POLICY
   Pralatrexate HIM – 6 months for Folotyn 20 mg/1 mL (refer to HIM.PA.103 for Folotyn 40 mg/2 mL if pharmacy benefit) Commercial – 6 months or to the member’s renewal date, whichever is longer
   B. NCCN-Recommended Off-Label Indications (must meet all):

3. Diagnosis of one of the following conditions (a or b): a. Primary cutaneous T-cell lymphomas (i or ii): i. Mycosis fungoides or Sézary syndrome; ii. Primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions, or cutaneous ALCL with regional nodes; b. Other T-cell lymphomas (i, ii, iii, or iv): i. Adult T-cell leukemia/lymphoma (ATLL) after failure of first-line therapy (see Appendix B for examples); ii. Extranodal NK/T-cell lymphoma (NKTL) following asparaginase-based therapy (see Appendix B for examples); iii. Hepatosplenic gamma-delta T-cell lymphoma (HGTL) after failure of 2 prior treatment regimens (see Appendix B for examples); iv. Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) after failure of first-line therapy (see Appendix B for examples); *Prior authorization may be required for prior line therapies
4. Prescribed by or in consultation with an oncologist or hematologist;
   
   3. Age ≥ 18 years;
   4. 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 – 6 months
      HIM – 6 months for Folotyn 20 mg/1 mL (refer to HIM.PA.103 for Folotyn 40 mg/2 mL if pharmacy benefit) Commercial – 6 months or to the member’s renewal date, whichever is longer
      C. 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 Page 2 of 8

   CLINICAL POLICY
   Pralatrexate 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):

7. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Folotyn for a covered indication and has received this medication for at least 30 days;
8. Member is responding positively to therapy;
   3. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 30 mg/m2 once weekly for 6 weeks in 7-week cycles; 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 – 12 months
      HIM – 12 months for Folotyn 20 mg/1 mL (refer to HIM.PA.103 for Folotyn 40 mg/2 mL if pharmacy benefit) Commercial – 6 months or to the member’s renewal date, whichever is longer
      B. Other diagnoses/indications (must meet 1 or 2):
9. 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

10. 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. Page 3 of 8

    CLINICAL POLICY
    Pralatrexate IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ALCL: anaplastic large cell lymphoma ATLL: adult T-cell leukemia/lymphoma BI-ALCL: breast implant-associated anaplastic large cell lymphoma FDA: Food and Drug Administration HGTL: hepatosplenic gamma-delta T-cell lymphoma NCCN: National Comprehensive Cancer Network NKTL: extranodal NK/T-cell lymphoma PTCL: peripheral T-cell lymphoma 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 Varies Dose Limit/ Maximum Dose Varies PTCL - examples of first-line and subsequent therapy: • Brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, and prednisone) • CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) • Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) • DHAP (dexamethasone, cisplatin, cytarabine) • ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) • Belinostat, brentuximab vedotin, romidepsin as single agents ATLL - examples of first-line therapy: • Brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, and prednisone) • CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) • Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) • HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) alternating with high-dose methotrexate and cytarabine NKTL - examples of asparaginase-based therapy: • AspaMetDex (pegaspargase, methotrexate, dexamethasone) Page 4 of 8 Varies Varies Varies Varies

    CLINICAL POLICY
    Pralatrexate Drug Name • DDGP (dexamethasone, cisplatin, gemcitabine, pegaspargase) • Modified-SMILE (steroid, methorexate, ifosfamide, pegaspargase, etoposide) • P-GEMOX (gemcitabine, pegaspargase, oxaliplatin) HGTL - examples of first-line therapy (for subsequent therapy examples see PTCL): • • CHOEP (cyclophosphamide, doxorubicin, vincristine, ICE (ifosfamide, carboplatin, etoposide) etoposide, prednisone) • Brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, and prednisone) BI-ALCL - examples of first-line therapy: • Brentuximab vedotin • Brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, and prednisone) • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) • CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) • Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) Dosing Regimen Dose Limit/ Maximum Dose Varies 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 None reported Appendix D: PTCL Subtypes/Histologies • PTCL, not otherwise specified • Anaplastic large cell lymphoma • Angioimmunoblastic T-cell lymphoma
    • Enteropathy-associated T-cell lymphoma
    • Monomorphic epitheliotropic intestinal T-cell lymphoma • Nodal peripheral T-cell lymphoma with TFH phenotype
    • Follicular T-cell lymphoma ____ PTLC is classified as a non-Hodgkin T-cell lymphoma. PTCL 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 PTCL. Page 5 of 8

    CLINICAL POLICY
    Pralatrexate V. Dosage and Administration
    Indication Dosing Regimen PTCL 30 mg/m2 IV once weekly for 6 weeks in 7-week cycles until progressive disease or unacceptable toxicity VI. Product Availability
    Single-dose vial: 20 mg/1 mL, 40 mg/2 mL Maximum Dose 30 mg/m2 once weekly VII.