XPOVIO, Selinexor Form

Selinexor (Xpovio®) is a nuclear export inhibitor (XPO1 inhibitor).
FDA Approved Indication(s) Xpovio is indicated: • • In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy. In combination with dexamethasone for the treatment of adult patients with relapsed or refractory MM who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐ CD38 monoclonal antibody. • For the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. 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).
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 Xpovio 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 or hematologist;
   3. Age ≥ 18 years;
   4. For Xpovio requests; member must use selinexor, if available, unless contraindicated or clinically significant adverse effects are experienced;

2. Disease is relapsed, refractory, or progressive;

   6. One of the following (a, b, c, d, or e):* a. Prescribed in combination with bortezomib and dexamethasone; b. Prescribed in combination with Darzalex®/Darzalex Faspro™ and dexamethasone; c. Prescribed in combination with carfilzomib and dexamethasone; Page 1 of 7

   CLINICAL POLICY Selinexor
   d. Prescribed in combination with pomalidomide and dexamethasone and member has received at least two prior therapies including an immunomodulatory agent and a proteasome inhibitor; e. Prescribed in combination with dexamethasone and member has received ≥ 4 prior therapies (see Appendix B) including all of the following (i, iii, and iii): i. Two proteasome inhibitors (e.g., bortezomib, Kyprolis®, Ninlaro®); ii. Two immunomodulatory agents (e.g., Revlimid®, pomalidomide, Thalomid®); iii. One anti CD38 monoclonal antibody (e.g., Darzalex®); *Prior authorization may be required for the agents listed above

3. Request meets one of the following (a or b):
   ‐ a. Dose does not exceed one of the following (i or ii): i. Prescribed in combination with bortezomib and dexamethasone: 100 mg (5 tablets) per week; ii. All other combination regimens: 160 mg (8 tablets) per week; 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/HIM – 6 months Legacy Wellcare – 12 months Commercial – 12 months or duration of request, whichever is less B. Diffuse Large B-Cell Lymphoma (must meet all):
4. Diagnosis of DLBCL, NOS, including DLBCL arising from follicular lymphoma or indolent lymphomas, AIDS-related DLBCL, primary effusion lymphoma, HHV8- positive DLBCL NOS;
5. Prescribed by or in consultation with an oncologist or hematologist;
   
   3. Age ≥ 18 years;
   4. For Xpovio requests; member must use selinexor, if available, unless contraindicated or clinically significant adverse effects are experienced;
6. Disease is relapsed, refractory (no or partial response), or progressive;
   6. Member has received ≥ 2 prior therapies (see Appendix B); Prior authorization may be required
7. Request meets one of the following (a or b): a. Dose does not exceed 60 mg (3 tablets) twice weekly; 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/HIM – 6 months Legacy Wellcare – 12 months Commercial – 12 months or duration of request, whichever is less C. Other diagnoses/indications (must meet 1 or 2):

8. 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 7

   CLINICAL POLICY Selinexor
   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

9. 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):
10. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Xpovio for a covered indication and has received this medication for at least 30 days;
11. Member is responding positively to therapy;
    3. For Xpovio requests; member must use selinexor, if available, unless contraindicated or clinically significant adverse effects are experienced;
12. If request is for a dose increase, request meets one of the following (a, b, or c):
    a. For MM: New dose does not exceed one of the following (i or ii):
    i. Prescribed in combination with bortezomib and dexamethasone: 100 mg (5 tablets) per week; ii. All other combination regimens: 160 mg (8 tablets) per week; b. For DLBCL: New dose does not exceed 60 mg (3 tablets) twice weekly; c. 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/HIM – 12 months Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

13. 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: Page 3 of 7

    CLINICAL POLICY Selinexor
    CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

14. 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 DLBCL: diffuse large B-cell lymphoma FDA: Food and Drug Administration MM: multiple myeloma NCCN: National Comprehensive Cancer Network NOS: not otherwise specified 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 MM: regimens containing proteasome inhibitors, immunomodulatory agents and/or anti- CD38 monoclonal antibodies (examples - NCCN) bortezomib / Revlimid (lenalidomide) or pomalidomide or Thalomid (thalidomide) / dexamethasone Kyprolis (carfilzomib – weekly or twice weekly) / dexamethasone Kyprolis / Revlimid / dexamethasone Ninlaro (ixazomib) / Revlimid / dexamethasone Darzalex (daratumumab) / bortezomib / dexamethasone ± Thalomid
    Darzalex / Revlimid / dexamethasone DLBCL NOS: second-line/subsequent regimens (examples - NCCN)
    GemOx (gemcitabine, oxaliplatin) ± rituximab Polatuzumab vedotin ± rituximab ± bendamustine DHAP (dexamethasone, cisplatin, cytarabine) ± rituximab DHAX (dexamethasone, cytarabine, oxaliplatin) ± rituximab Yescarta® (axicabtagene ciloleucel)
    Kymriah® (tisagenlecleucel) Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Page 4 of 7

    CLINICAL POLICY Selinexor
    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
    V. Dosage and Administration
    Indication MM Dosing Regimen 80 mg in combination with dexamethasone PO on days 1 and 3 of each week Maximum Dose 160 mg/week 100 mg in combination with bortezomib and dexamethasone PO on day 1 of each week 60 mg PO on Days 1 and 3 of each week 60 mg/day DLBCL VI. Product Availability
    Tablet: 20 mg, 40 mg, 50 mg, 60 mg VII.