EMPLICITI, Elotuzumab Form

Elotuzumab (Empliciti®) is a SLAMF7-directed immunostimulatory antibody. FDA Approved Indication(s) Empliciti is indicated in combination with: • Lenalidomide and dexamethasone for the treatment of patients with multiple myeloma (MM) who have received one to three prior therapies • Pomalidomide and dexamethasone for the treatment of adult patients with MM who have received at least two prior therapies including lenalidomide and a proteasome inhibitor 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 Empliciti is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Multiple Myeloma (must meet all):

1. Diagnosis of MM;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Member has received ≥ 1 prior therapy (see Appendix B for examples);
   5. Empliciti is prescribed in combination with dexamethasone, and either Pomalyst®, lenalidomide, or bortezomib;Prior authorization may be required for Pomalyst, lenalidomide , and bortezomib.

2. Request meets one of the following (a or b): a. Dose does not exceed (i or ii): i. With lenalidomide, both of the following (1 and 2):
   1) 10 mg/kg per week for the first two cycles (4 doses per 28-day cycle);
   2) 10 mg/kg per 2 weeks (2 doses per 28-day cycle) for subsequent cycles; ii. With Pomalyst, both of the following (1 and 2):
   1) 10 mg/kg every week for the first 2 cycles (4 doses per 28-day cycle);
   2) 20 mg/kg every 4 weeks (1 dose per 28-day cycle) for subsequent 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
   Page 1 of 8

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

3. 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
4. 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):
5. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Empliciti for a covered indication and has received this medication for at least 30 days;
6. 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 or ii): i. With lenalidomide, both of the following (1 and 2):
      1) 10 mg/kg per week for the first two cycles (4 doses per 28-day cycle);
      2) 10 mg/kg per 2 weeks (2 doses per 28-day cycle) for subsequent cycles; ii. With Pomalyst, both of the following (1 and 2):
      1) 10 mg/kg every week for the first 2 cycles (4 doses per 28-day cycle);
      2) 20 mg/kg every 4 weeks (1 dose per 28-day cycle) for subsequent 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):

7. 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 Page 2 of 8

   CLINICAL POLICY Elotuzumab 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

8. 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 FDA: Food and Drug Administration MM: multiple myeloma NCCN: National Comprehensive Cancer 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 bortezomib (Velcade) Empliciti in combination with Velcade and dexamethasone: • Regimens vary.
   • Per NCCN, the SC rather than IV bortezomib formulation is preferred. An SC generic formulation is not available. lenalidomide
   (Revlimid) Pomalyst (pomalidomide) Kyprolis® (carfilzomib), bortezomib (Velcade),
   Empliciti in combination with Revlimid and dexamethasone: Regimens vary.
   Empliciti in combination with Pomalyst and dexamethasone: Regimens vary. Examples of primary therapy • Bortezomib/dexamethasone • Bortezomib/lenalidomide/dexamethasone • Bortezomib/cyclophosphamide/dexamethasone Page 3 of 8

   Dose Limit/ Maximum Dose Varies CLINICAL POLICY Elotuzumab Drug Name Dosing Regimen lenalidomide (Revlimid), cyclophosphamide , dexamethasone Kyprolis (carfilzomib), bortezomib (Velcade),
   lenalidomide (Revlimid), Darzalex® (daratumumab), Ninlaro® (ixazomib), Pomalyst (pomalidomide), Empliciti® (elotuzumab),
   Thalomid® (thalidomide), bendamustine, cyclophosphamide , dexamethasone, Sarclisa® • Bortezomib/doxorubicin/dexamethasone • Bortezomib/thalidomide/dexamethasone • Carfilzomib/cyclophosphamide/dexamethasone • Carfilzomib/lenalidomide/dexamethasone • Cyclophosphamide/lenalidomide/dexamethasone • Daratumumab/lenalidomide/dexamethasone • Daratumumab/lenalidomide/bortezomib/ dexamethasone • Daratumumab/carfilzomib/lenalidomide/ dexamethasone • Daratumumab/cyclophosphamide/bortezomib/ dexamethasone • Daratumumab/bortezomib/thalidomide/ dexamethasone • Daratumumab/bortezomib/melphalan/prednisone • Dexamethasone/thalidomide/cisplatin/doxorubicin/ cyclophosphamide/etoposide/bortezomib (VTD- PACE) • Ixazomib/cyclophosphamide/dexamethasone • Ixazomib/lenalidomide/dexamethasone • Lenalidomide/low-dose dexamethasone Examples of therapy for previously treated for relapsed or refractory disease: • Bendamustine • Bendamustine/bortezomib/dexamethasone • Bendamustine/lenalidomide/dexamethasone • Bendamustine/carfilzomib/dexamethasone • Bortezomib/dexamethasone • Bortezomib/lenalidomide/dexamethasone • Bortezomib/liposomal doxorubicin/dexamethasone • Bortezomib/cyclophosphamide/dexamethasone • Carfilzomib/cyclophosphamide/dexamethasone • Carfilzomib/dexamethasone • Carfilzomib/lenalidomide/dexamethasone • Carfilzomib/cyclophosphamide/dexamethasone • Carfilzomib/cyclophosphamide/thalidomide/ dexamethasone • Cyclophosphamide/lenalidomide/dexamethasone • Cyclophosphamide • Daratumumab Page 4 of 8

   CLINICAL POLICY Elotuzumab Drug Name Dosing Regimen (istatuximab-irfc), Xpovio® (selinexor) • Daratumumab/bortezomib/dexamethasone • Daratumumab/carfilzomib/dexamethasone • Daratumumab/cyclophosphamide/bortezomib/ Dose Limit/ Maximum Dose dexamethasone • Daratumumab/lenalidomide/dexamethasone • Daratumumab/pomalidomide/dexamethasone • Dexamethasone/cyclophosphamide/etoposide/cisplati n • Dexamethasone/thalidomide/cisplatin/doxorubicin/cy clophosphamide/etoposide/ +/- bortezomib • Elotuzumab/lenalidomide/dexamethasone • Elotuzumab/bortezomib/dexamethasone • Elotuzumab/pomalidomide/dexamethasone • Istatuximab-irfc/carfilzomib/dexamethasone • Ixazomib/cyclophosphamide/dexamethasone • Ixazomib/lenalidomide/dexamethasone • Ixazomib/pomalidomide/desamethasone • Isatuximab-irfc/pomalidomide/dexamethasone • Lenalidomide/dexamethasone • Pomalidomide/bortezomib/dexamethasone • Pomalidomide/carfilzomib/dexamethasone • Pomalidomide/cyclophosphamide/dexamethasone • Pomalidomide/dexamethasone • Selinexor/bortezomib/dexamethasone • Selinexor/carfilzomib/dexamethasone • Selinexor/daratumumab/dexamethasone • Selinexor/opomalidomide/dexamthasone • Venetoclax/dexamethasone • Ideocabtagene vicleucel • Ciltacabtagene autoleucel • Teclistamab-cqyv • Benlantamab mafodotin-blmf
   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/Black Box Warnings None reported Page 5 of 8

   Maximum Dose With lenalidomide:
   10 mg/kg
   With pomalidomide: 20 mg/kg CLINICAL POLICY Elotuzumab V. Dosage and Administration
   Indication Dosing Regimen MM Cycles one and two: • Empliciti: 10 mg/kg IV once weekly on cycles 1 and 2 (on days 1, 8, 15, and 22),
   • Dexamethasone: 28 mg PO between 3 and 24 hours before Empliciti plus 8 mg IV between 45 and 90 minutes before Empliciti • Lenalidomide: 25 mg PO QD x 21 days of a 28-day cycle OR • Pomalidomide: 4 mg PO QD x 21 days of a 28-day cycle Cycles three and beyond:
   • Empliciti:
   o With lenalidomide: 10 mg/kg IV once every 2 weeks (on days 1 and 15) o With pomalidomide: 20 mg/kg IV once every 4 weeks
   • Dexamethasone: Administer as for cycles one and two and on the days Empliciti is not given (days 8 and 22), give 40 mg PO QD if 75 years or younger OR 20 mg PO QD if older than 75 years • Lenalidomide: 25 mg PO QD x 21 days of a 28-day cycle OR • Pomalidomide: 4 mg PO QD x 21 days of a 28-day VI. Product Availability
   Single-dose vial: 300 mg, 400 mg VII.