ADCETRIS, Brentuximab Vedotin Form

Brentuximab vedotin for injection (Adcetris®) is a CD30-directed antibody-drug conjugate. FDA Approved Indication(s) Adcetris is indicated for the treatment of adult patients with: • Classical Hodgkin lymphoma: o Previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine o cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation
o cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates • T-cell lymphomas: o Previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30- expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone o sALCL after failure of at least one prior multiagent chemotherapy regimen • Primary cutaneous lymphomas: o Primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy Adcetris is indicated for the treatment of pediatric patients 2 years old and older with: • Classical Hodgkin lymphoma: o Previously untreated high risk classical Hodgkin lymphoma, in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide 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 Adcetris is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Classical Hodgkin Lymphoma in Adults (must meet all):

1. Diagnosis of cHL; Page 1 of 10

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   Brentuximab Vedotin

2. Prescribed by or in consultation with an oncologist or hematologist; Age ≥ 18 years; If the age is between 2 to 21 years, consider using criteria B below for cHL in Pediatric and Adolescent Patients.
3. Request meets one of the following (a or b): a. Dose does not exceed (i, ii, or iii): i. Previously untreated Stage III or IV cHL: 1.2 mg/kg up to 120 mg every 2 weeks for a maximum of 12 doses;
   ii. cHL consolidation: 1.8 mg/kg up to 180 mg every 3 weeks for a maximum of 16 cycles; iii. Relapsed cHL: 1.8 mg/kg up to 180 mg every 3 weeks; 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
   B. Classical Hodgkin Lymphoma in Pediatric and Adolescent Patients (must meet all):
   1. Diagnosis of previously untreated pathologically confirmed cHL meeting one of the following Ann Arbor stages (a, b, c or d): a. Stage IIB with bulk tumor (see Appendix D for the definition of Bulk Disease); b. Stage IIIB; c. Stage IVA; d. Stage IVB;
4. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 2 years to 21 years;
   4. Request meets one of the following (a or b): a. Dose does not exceed: 1.8 mg/kg up to 180 mg every 3 weeks for a maximum of 5 doses;
      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
      C. T-Cell Lymphomas (must meet all):

5. Diagnosis of one of the following (a, b, c, d, or e): a. PTCL - any of the following subtypes/histologies (i or ii): i. sALCL;
   ii. PTCL, including but not limited to the following (a, b, c, d, or e): a) Angioimmunoblastic T-cell lymphoma; b) Enteropathy-associated T-cell lymphoma; c) Monomorphic epitheliotropic intestinal T-cell lymphoma; d) Nodal PTCL with TFH phenotype; e) Follicular T-cell lymphoma; b. Breast implant-associated ALCL (off-label); c. Adult T-cell leukemia/lymphoma (off-label); d. Relapsed or refractory extranodal NK/T-cell lymphoma (off-label); Page 2 of 10

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   Brentuximab Vedotin e. Hepatosplenic T-cell lymphoma after failure of two first-line therapy regimens (off-label);

6. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Disease is CD30-positive;
   5. Request meets one of the following (a, b, or c): a. Previously untreated sALCL or other CD30-positive PTCL including angioimmunoblastic T-cell lymphoma: Dose does not exceed 1.8 mg/kg up to 180 mg every 3 weeks with each cycle of chemotherapy for 6 to 8 doses; b. Relapsed sALCL: Dose does not exceed 1.8 mg/kg up to 180 mg every 3 weeks; c. 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. Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders (must meet all):
7. Diagnosis of one of the following (a, b, or c): a. pcALCL; b. Cutaneous ALCL and lymph node positive (off-label); c. Lymphomatoid papulosis - as subsequent therapy for relapsed/refractory disease (off-label);

8. Prescribed by or in consultation with an oncologist or hematologist;

   3. Age ≥ 18 years;
   4. Disease is CD30-positive;
   5. Request meets one of the following (a or b): a. Relapsed pcALCL: Dose does not exceed 1.8 mg/kg up to 180 mg every 3 weeks for a maximum of 16 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: 6 months E. Mycosis Fungoides/Sezary Syndrome (must meet all):
   6. Diagnosis of MF or Sezary syndrome (off-label);
   7. Prescribed by or in consultation with an oncologist or hematologist;
   8. Age ≥ 18 years;
   9. Disease is CD30-positive;
   10. Request meets one of the following (a or b): a. Relapsed CD30-positive MF: Dose does not exceed 1.8 mg/kg up to 180 mg every 3 weeks for a maximum of 16 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: 6 months F. B-Cell Lymphomas (off-label) (must meet all):
   11. Diagnosis of one of the following (a or b): Page 3 of 10

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   Brentuximab Vedotin a. Diffuse large B-cell lymphoma, including but not limited to (i, ii, or iii): i. Follicular lymphoma that has undergone histologic transformation to diffuse large B-cell lymphoma; ii. Marginal zone lymphoma that has undergone histologic transformation to diffuse large B-cell lymphoma; iii. Primary mediastinal large B-cell lymphoma; b. High-grade B-cell lymphoma; c. AIDS-related B-cell lymphoma; d. Post-transplant lymphoproliferative disorder - monomorphic PTLD (T-cell type);

9. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Disease is CD30-positive;
   5. For subtypes other than monomorphic PTLD (T-cell type), Adcetris is prescribed as subsequent therapy;
10. 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: 6 months G. 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.
    II. Continued Therapy A. All Indications in Section I (must meet all):
13. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Adcetris for a covered indication and has received this medication for at least 30 days;

14. 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 (i, ii, iii, iv, v, vi, vii or viii):
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    Brentuximab Vedotin i. Previously untreated Stage III or IV cHL in adults: 1.2 mg/kg up to 120 mg every 2 weeks for a maximum of 12 doses;
    ii. Previously untreated high risk cHL in pediatric and adolescent patients: 1.8 mg/kg up to 180 mg every 3 weeks for a maximum of 5 doses; iii. cHL consolidation in adults: 1.8 mg/kg up to 180 mg every 3 weeks for a maximum of 16 cycles; iv. Relapsed cHL in adults: 1.8 mg/kg up to 180 mg every 3 weeks; v. Previously untreated sALCL or other CD30-positive PTCL including angioimmunoblastic T-cell lymphoma in adults: 1.8 mg/kg up to 180 mg every 3 weeks with each cycle of chemotherapy for 6 to 8 doses; vi. Relapsed sALCL in adults: 1.8 mg/kg up to 180 mg every 3 weeks; vii. Relapsed pcALCL in adults: 1.8 mg/kg up to 180 mg every 3 weeks for a maximum of 16 cycles; viii. Relapsed CD30-positive MF in adults: 1.8 mg/kg up to 180 mg every 3 weeks for a maximum of 16 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: 12 months B. Other diagnoses/indications (must meet 1 or 2):

15. 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 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

16. 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 2 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 policy – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents. Page 5 of 10

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    Brentuximab Vedotin IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key cHL: classical Hodgkin lymphoma FDA: Food and Drug Administration HSCT: hematopoietic stem cell transplantation pcALCL: primary cutaneous anaplastic large cell lymphoma PTCL: peripheral T-cell lymphoma sALCL: systemic analplastic large cell MF: mycosis fungoides NCCN: National Comprehensive Cancer lymphoma SS: Sezary syndrome Network Appendix B: Therapeutic Alternatives
    Not applicable Appendix C: Contraindications/Boxed Warnings • Contraindication(s): concomitant use with bleomycin due to pulmonary toxicity • Boxed warning(s): progressive multifocal leukoencephalopathy Appendix D: Definition of Bulk Disease Bulk disease is defined as: • Large mediastinal adenopathy (LMA): a mediastinal mass where the tumor diameter is > 1/3 the maximal thoracic diameter on an upright posteroanterior (PA) chest radiograph; • Large extra-mediastinal nodal aggregate: a contiguous extramediastinal nodal aggregate that measures > 6 cm in the longest transverse diameter (transaxial measurement) or craniocaudal dimension (measured on reformatted computed tomography). V. Dosage and Administration
    Indication Dosing Regimen Previously untreated Stage III or IV cHL in adults Previously untreated high risk cHL in pediatric and adolescent patients cHL consolidation in adults Relapsed cHL in adults 1.2 mg/kg IV up to a maximum of 120 mg in combination with chemotherapy. Administer every 2 weeks until a maximum of 12 doses, disease progression, or unacceptable toxicity. 1.8 mg/kg IV up to a maximum of 180 mg in combination with chemotherapy. Administer every 3 weeks with each cycle of chemotherapy for a maximum of 5 doses, disease progression, or unacceptable toxicity. 1.8 mg/kg IV up to a maximum of 180 mg. Initiate Adcetris treatment within 4-6 weeks post-autoHSCT or upon recovery from auto-HSCT. Administer every 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity. 1.8 mg/kg IV up to a maximum of 180 mg. Administer every 3 weeks until disease progression or unacceptable toxicity. Maximum Dose 120 mg every 2 weeks up to 12 doses 180 mg every 3 weeks up to 5 doses 180 mg every 3 weeks up to 16 cycles 180 mg every 3 weeks Page 6 of 10

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    Brentuximab Vedotin Indication Dosing Regimen 1.8 mg/kg IV up to a maximum of 180 mg in combination with cyclophosphamide, doxorubicin, and prednisone. Administer every 3 weeks with each cycle of chemotherapy for 6 to 8 doses. Maximum Dose 180 mg every 3 weeks up to 6 to 8 doses 1.8 mg/kg IV up to a maximum of 180 mg. Administer every 3 weeks until disease progression or unacceptable toxicity. 1.8 mg/kg IV up to a maximum of 180 mg. Administer every 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity. 180 mg every 3 weeks 180 mg every 3 weeks up to 16 cycles Previously untreated sALCL or other CD30- expressing PTCLs in adults Relapsed sALCL in adults Relapsed pcALCL or CD30- expressing MF in adults VI. Product Availability
    Single-use vial: 50 mg for reconstitution VII.