Belantamab Mafodotin (Blenrep) Form

Belantamab mafodotin-blmf (Blenrep®) is an anti-B-cell maturation antigen (BCMA) monoclonal antibody and microtubule inhibitor conjugate. FDA Approved Indication(s)
Blenrep is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy, including an anti-CD38 antibody, a proteasome inhibitor, and an immunomodulatory agent. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). _ GlaxoSmithKline (GSK), the manufacturer of Blenrep, voluntarily withdrew Blenrep after post-market data from the DREAMM-3 Phase 3 trial revealed Blenrep did not meet the requirements of the FDA Accelerated Approval regulation. The FDA withdrew its approval for the product (see Appendix D). 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 Blenrep is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Multiple Myeloma (must meet all):

1. Provider attestation of acknowledgement of FDA’s request for withdrawal of product due to failure to demonstrate superior progression-free survival (PFS) compared to placebo;

2. Diagnosis of multiple myeloma;

   3. Prescribed by or in consultation with an oncologist or hematologist;
   4. Age ≥ 18 years;
   5. Blenrep is prescribed as monotherapy;
   6. Member has received ≥ 4 prior lines of therapy (see Appendix B for examples) that include all of the following (a, b, and c): a. One proteasome inhibitor (e.g., bortezomib, Kyprolis®, Ninlaro®); b. One immunomodulatory agent (e.g., Revlimid®, pomalidomide, Thalomid®); c. One anti-CD38 antibody (e.g., Darzalex®/Darzalex Faspro™, Sarclisa®); Page 1 of 8

   CLINICAL POLICY Belantamab Mafodotin-blmf *Prior authorization may be required

3. Request meets one of the following (a or b): a. Dose does not exceed 2.5 mg/kg 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. Other diagnoses/indications (must meet 1 or 2):
4. 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
5. 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. Multiple Myeloma (must meet all):
6. Provider attestation of acknowledgement of FDA’s request for withdrawal of product due to failure to demonstrate superior PFS compared to placebo;
7. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Blenrep for a covered indication and has received this medication for at least 30 days;
8. Member is responding positively to therapy;
   4. Dose is ≥ 1.9 mg/kg every 3 weeks;
   5. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 2.5 mg/kg every 3 weeks; 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):

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): Page 2 of 8

   CLINICAL POLICY Belantamab Mafodotin-blmf 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. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key BCMA: B-cell maturation antigen FDA: Food and Drug Administration GSK: GlaxoSmithKline PFS: progression free survival 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 bortezomib/Revlimid® (lenalidomide)/dexamethasone bortezomib/cyclophosphamide/dexamethasone bortezomib/doxorubicin (or liposomal doxorubicin)/ dexamethasone Kyprolis® (carfilzomib) Revlimid® (lenalidomide)/ dexamethasone Kyprolis® (carfilzomib)/cyclophosphamide/ dexamethasone Kyprolis® (carfilzomib – weekly or twice weekly)/ dexamethasone Ninlaro® (ixazomib)/Revlimid® (lenalidomide)/ dexamethasone Ninlaro® (ixazomib)/dexamethasone Ninlaro® (ixazomib)/pomalidomide/dexamethasone bortezomib/dexamethasone Page 3 of 8 Dosing Regimen Varies Varies Varies Dose Limit/ Maximum Dose Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies

    CLINICAL POLICY Belantamab Mafodotin-blmf Drug Name Dosing Regimen Varies Varies Dose Limit/ Maximum Dose Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies bortezomib/Thalomid® (thalidomide)/dexamethasone cyclophosphamide/Revlimid® (lenalidomide)/ dexamethasone Revlimid® (lenalidomide)/dexamethasone VTD-PACE (dexamethasone/Thalomid® (thalidomide)/ cisplatin/doxorubicin/cyclophosphamide/etoposide/ bortezomib) Revlimid® (lenalidomide)/low-dose dexamethasone Darzalex® (daratumumab) or Darzalex Faspro™ (daratumumab/hyaluronidase-fihj)/bortezomib/ melphan/prednisone Darzalex® (daratumumab) or Darzalex Faspro™ (daratumumab/hyaluronidase-fihj)/ bortezomib/dexamethasone Darzalex® (daratumumab) or Darzalex Faspro™ (daratumumab/hyaluronidase-fihj)/Revlimid® (lenalidomide)/dexamethasone Darzalex® (daratumumab) or Darzalex Faspro™ (daratumumab/hyaluronidase-fihj) Darzalex® (daratumumab) or Darzalex Faspro™ (daratumumab/hyaluronidase-fihj)/pomalidomide/ dexamethasone Empliciti® (elotuzumab)/Revlimid® (lenalidomide)/ dexamethasone Empliciti® (elotuzumab)/bortezomib/dexamethasone Varies Empliciti® (elotuzumab)/pomalidomide/dexamethasone Varies Varies bendamustine/bortezomib/dexamethasone bendamustine/Revlimid® (lenalidomide)/ Varies dexamethasone panobinostat/bortezomib/dexamethasone Varies panobinostat/Kyprolis® (carfilzomib) Varies panobinostat/Revlimid® (lenalidomide)/dexamethasone Varies Varies pomalidomide/cyclophosphamide/dexamethasone Varies pomalidomide/dexamethasone pomalidomide/bortezomib/dexamethasone Varies pomalidomide/Kyprolis® (carfilzomib)/dexamethasone Varies Sarclisa® (isatuximab-irfc)/pomalidomide/ Varies dexamethasone 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 Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): ocular toxicity Page 4 of 8

    CLINICAL POLICY Belantamab Mafodotin-blmf o In clinical studies, Blenrep caused changes in the corneal epithelium resulting in changes in vision, including severe vision loss and corneal ulcer, and symptoms, such as blurred vision and dry eyes. Because of these risks, Blenrep is only available through a restricted program, called the Blenrep REMS. Appendix D: Withdrawal from Market • GSK, the manufacture of Blenrep, voluntarily withdrew Blenrep after post-market data from the DREAMM-3 Phase 3 trial revealed Blenrep did not meet the requirements of the FDA Accelerated Approval regulation.
    o Blenrep did not meet its primary endpoint of superior PFS compared to pomalidomide and dexamethasone (PomDex) for relapsed or refractory multiple myeloma. o The hazard ratio for PFS was 1.03 (95% CI: 0.72, 1.47). However, the observed median PFS was longer for Blenrep vs PomDex (11.2 vs 7 months).
    • GSK has stopped new patient enrollment (as of November 22, 2022) into the Blenrep REMS.
    • GSK recommends prescribers discuss the individual risk vs benefits to decide ongoing care. • For enrolled patients deriving clinical benefits, Blenrep will continue to be available until GSK launces compassionate use program.
    o Details on compassionate use program will be provided directly to REMS enrolled prescriber.
    • GSK recommends patients currently being treated with Blenrep should consult their healthcare providers. V. Dosage and Administration Dosing Regimen Indication 2.5 mg/kg IV infusion every 3 weeks until disease Multiple progression or unacceptable toxicity myeloma If dose reduction to < 1.9 mg/kg is required, discontinue therapy. Maximum Dose 2.5 mg/kg/dose VI. Product Availability
    Lyophilized powder in a single-dose vial for reconstitution and further dilution for injection: 100 mg VII.