POLIVY, Polatuzumab Vedotin-piiq Form

Polatuzumab vedotin-piiq (Polivy™) is a CD79b-directed antibody-drug conjugate with activity against dividing B cells. FDA Approved Indication(s) Polivy is indicated in combination with bendamustine and a rituximab product for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), after at least two prior therapies. Accelerated approval was granted for this indication based on complete response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. 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 Polivy is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Diffuse Large B-Cell Lymphoma (must meet all):

1. Diagnosis of DLBCL (see subtypes at Appendix D);
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Member is not a candidate for allogeneic or autologous stem cell transplant;
   5. Member has received ≥ 1 prior therapy (see Appendix B);
   6. Polivy is prescribed as a single agent or in combination with bendamustine and/or a rituximab product (see Appendix B for rituximab products); *Prior authorization may be required for bendamustine and rituximab products

2. Request meets one of the following (a or b): a. Dose does not exceed 1.8 mg/kg on Day 1 of a 21-day cycle, for a maximum of 6 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 (medical justification supports requests for cycles beyond 6)
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   CLINICAL POLICY Polatuzumab Vedotin-piiq
   B. NCCN Recommended Uses (off-label) (must meet all):

   1. Diagnosis of one of the following (a, b, c, d, or e): a. Follicular lymphoma (FL) (grade 1-2); b. Mantle cell lymphoma; c. Monomorphic post-transplant lymphoproliferative disorder (B-cell type); d. One of the following AIDS-related B-cell lymphoma subtypes (i, ii, iii, or iv): i. AIDS-related DLBCL; ii. Primary effusion lymphoma; iii. HHV8-positive diffuse large B-cell lymphoma, NOS; iv. AIDS-related plasmablastic lymphoma; e. Histologic transformation of nodal marginal zone lymphoma to diffuse large B- cell lymphoma;
3. Prescribed by or in consultation with an oncologist or hematologist;
   
   3. Age ≥ 18 years;
   4. For requests other than FL grade 1-2, member is not a candidate for allogeneic or autologous stem cell transplant;
4. Member has received ≥ 1 prior therapy (see Appendix B);
   6. Polivy is prescribed as a single agent or in combination with bendamustine and/or a rituximab product (see Appendix B for rituximab products); *Prior authorization may be required for bendamustine and rituximab products
5. 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 (medical justification is required for requests for more than 6 cycles) 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.
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   CLINICAL POLICY Polatuzumab Vedotin-piiq
   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 Polivy for a covered indication and has received this medication for at least 30 days;
9. Member is responding positively to therapy;
   3. Member meets one of the following (a or b): a. Member has received < 6 cycles of Polivy; b. Member has received less than the number of cycles recommended by NCCN for the covered indication;
10. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 1.8 mg/kg on Day 1 of a 21-day cycle, for a maximum of 6 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 (medical justification supports requests for cycles beyond 6) 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. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key DLBCL: diffuse large B-cell lymphoma FDA: Food and Drug Administration FL: follicular lymphoma HGBL: high-grade B-cell lymphoma Page 3 of 8

    CLINICAL POLICY Polatuzumab Vedotin-piiq
    NCCN: National Comprehensive Cancer NOS: not otherwise specified Network 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 Dose Limit/ Maximum Dose Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Rituximab Products Rituxan® (rituximab), Truxima® (rituximab-abbs), Rituxan Hycela® (rituximab-hyaluronidase) DLBCL Regimen examples (NCCN) bendamustine ± rituximab CEPP (cyclophosphamide, etoposide, prednisone, procarbazine) ± rituximab lenalidomide ± rituximab HGBL Regimen examples (NCCN) DA-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin + rituximab) RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) FL (grade 1-2) Regimen examples (NCCN) Anthracycline- or anthracenedione-based regimens: CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) + obinutuzumab or rituximab CVP (cyclophosphamide,vincristine, prednisone) + obinutuzumab or rituximab RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) Mantle Cell Lymphoma Regimen examples (NCCN) RDHA (rituximab, dexamethasone, cytarabine) + platinum (carboplatin, ciplatin, or oxaliplatin) VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone) Post-Transplant Lymphoproliferative Disorder Regimen examples (NCCN) CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) + obinutuzumab or rituximab CVP (cyclophosphamide,vincristine, prednisone) + obinutuzumab or rituximab AIDS-related B-Cell Lymphoma Regimen examples (NCCN) R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) + rituximab Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Page 4 of 8

    CLINICAL POLICY Polatuzumab Vedotin-piiq
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose Histologic Transformation of Nodal Marginal Zone Lymphoma to DLBCL Regimen examples (NCCN) RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) 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. Varies Varies Appendix C: Contraindications/Boxed Warnings None reported Intravascular large B-cell lymphoma Appendix D: DLBCL Subtypes per the National Comprehensive Cancer Network (NCCN) • DLBCL, NOS (FDA-approved use) • DLBCL coexistent with follicular lymphoma of any grade • DLBCL coexistent with gastric MALT lymphoma • DLBCL coexistent with nongastric MALT lymphoma • Follicular lymphoma grade 3 • • DLBCL associated with chronic inflammation • ALK-positive LBCL • EBV-positive DLBCL, NOS • T-cell/histiocyte-rich large B-cell lymphoma • LBCL with IRF4/MUM1 rearrangement • Double expressor DLBCL • Primary mediastinal LBCL • Gray zone lymphoma • High-grade B-cell lymphomas with translocations of MYC and BCL2 and/or BCL6 • High-grade B-cell lymphomas, NOS • Primary cutaneous DLBCL Maximum Dose 1.8 mg/kg (Polivy) V. Dosage and Administration
    Indication DLBCL Dosing Regimen 1.8 mg/kg IV over 90 minutes every 21 days for 6 cycles in combination with bendamustine and a rituximab product. (Administer Polivy, bendamustine, and rituximab product in any order on Day 1 of each cycle.) • Bendamustine: The recommended dose of bendamustine is 90 mg/m2/day IV on Day 1 and 2 when administered with Polivy and a rituximab product.
    • Rituximab product: The recommended dose of rituximab product is 375 mg/m2 IV on Day 1 of each cycle. Page 5 of 8

    CLINICAL POLICY Polatuzumab Vedotin-piiq
    VI. Product Availability
    Single-dose vial for injection after reconstitution: 30 mg, 140 mg
    VII.