CurrentCentenePolicy CP.PHAR.431

Selinexor (Xpovio) — Clinical Policy

Defines medical necessity criteria, dosing limits, and authorization requirements for selinexor (Xpovio) for multiple myeloma and B-cell lymphomas for Centene lines of business (Commercial, HIM, Medicaid). Applies to prescribers requesting coverage under Centene benefits.

Policy Summary

PayerCentene

PolicySelinexor (Xpovio) — Clinical Policy

Policy CodePolicy CP.PHAR.431

Change TypeNo material change

Effective DateJul 16, 2019

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results or other clinical information) demonstrating the member meets all approval criteria for selinexor.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

2FDA-approved disease indications listed

12 monthsTypical approval duration

160 mgMM max weekly dose

120 mgB-cell lymphoma dose limit

Coverage Criteria

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MM initial approval: 1) Diagnosis of multiple myeloma; 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 18 years; 4) For Xpovio requests, member must use selinexor (Xpovio) if available unless contraindicated or clinically significant adverse effects are experienced; 5) Disease is relapsed, refractory, or progressive; 6) One of the following concomitant regimens: a) prescribed in combination with bortezomib and dexamethasone; b) prescribed in combination with daratumumab (Darzalex/Darzalex Faspro) and dexamethasone; c) prescribed in combination with carfilzomib (Kyprolis) and dexamethasone; 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 including two proteasome inhibitors, two immunomodulatory agents, and one anti-CD38 monoclonal antibody; 7) Requested dose does not exceed regimen-specific weekly limits: i) with bortezomib + dexamethasone: 100 mg per week (5 tablets/week); ii) all other combination regimens: 160 mg per week (8 tablets/week); or 8) Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).see node text

Prior authorization may be required for the listed concomitant agents; prescribed regimen must be FDA-approved or recommended by NCCN.

inv-02: Initial Therapy - B-cell Lymphoma

Covered when ALL of the following are met:

B-cell lymphoma initial approval: 1) Diagnosis of one of the following B-cell lymphomas: a) DLBCL, including DLBCL arising from indolent lymphomas; b) High-grade B-cell lymphoma (off-label); c) HIV-related B-cell lymphoma (including HIV-related DLBCL, primary effusion lymphoma, and HHV8-positive DLBCL NOS) (off-label); d) Monomorphic post-transplant lymphoproliferative disorder (B-cell type) (off-label); 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 18 years; 4) For Xpovio requests, member must use selinexor (Xpovio) if available unless contraindicated or clinically significant adverse effects are experienced; 5) Disease is relapsed, refractory (no or partial response), or progressive; 6) Member has received ≥ 2 prior therapies; 7) Requested dose does not exceed 120 mg per week (6 tablets/week) unless dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).120 mg/week

Prescribed regimen must be FDA-approved or recommended by NCCN; prior authorization may be required.

inv-03: Continuation Therapy

Covered for continuation when ALL of the following are met:

Continued therapy: 1) Member is currently receiving Xpovio via the Centene benefit, or documentation supports member has received Xpovio for a covered indication for at least 30 days; 2) Member is responding positively to therapy (clinical benefit); 3) For Xpovio requests, member must use selinexor if available unless contraindicated or clinically significant adverse effects are experienced; 4) If request is for a dose increase, new dose must meet one of the following: a) For MM: i) with bortezomib + dexamethasone: not to exceed 100 mg per week (5 tablets/week); ii) all other combination regimens: not to exceed 160 mg per week (8 tablets/week); b) For B-cell lymphomas: not to exceed 120 mg per week (6 tablets/week); c) New dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).see node text

Approval durations: Medicaid/HIM - 12 months; Commercial - 12 months or duration of request, whichever is less. Prescribed regimen must be FDA-approved or recommended by NCCN.

Requests for use of selinexor (Xpovio) for non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider submits sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies (Commercial: CP.CPA.09; Health Insurance Marketplace: HIM.PA.154; Medicaid: CP.PMN.53) or as specified in the member’s evidence of coverage.

Coding and Dose Limits

Dose limits

MM combination - bortezomib + dexamethasoneLimit: 100 mg per week (maximum 5 tablets per week)

MM combination - all other regimensLimit: 160 mg per week (maximum 8 tablets per week)

B‑cell lymphoma (including DLBCL)Limit: 120 mg per week (maximum 6 tablets per week); aligned from prior 60 mg twice-weekly wording

DLBCL example dosingExample regimen: 60 mg PO on Days 1 and 3 each week (per dosing examples)

Alternate MM dosing scheduleAlternate MM dosing: 80 mg PO on Days 1 and 3 weekly (documented regimen example)

Provider Actions and Requirements

Prior Authorization

Provider Actions and Requirements

Prior Authorization Required: Prior authorization is required. Provider must demonstrate that the member meets all applicable clinical criteria (diagnosis, prescriber specialty, age, prior therapies, regimen and dosing limits, and combination regimen requirements). Provider must submit supporting documentation (e.g., office chart notes, lab results, and other clinical information).

Prior authorization and approval duration: Initial approval durations and dosing limits are governed by the clinical criteria in this policy; changes to initial approval durations (including extension of Medicaid and HIM initial approval durations from 6 to 12 months for maintenance medications) are reflected in policy history and applied per plan.
Off-label/Non‑FDA approved indications: Requests for non‑FDA approved indications not addressed in this policy may be denied unless sufficient documentation of efficacy and safety is provided per off‑label use policies CP.CPA.09 (Commercial), HIM.PA.154 (HIM), and CP.PMN.53 (Medicaid) or per plan evidence of coverage.
Therapeutic alternatives referenced: Preferred or alternative agents and regimens are listed in Appendix B and in the Appendices/General Information (examples per NCCN); prior authorization may also be required for those agents.
Policy revisions: Policy revisions have included alignment with NCCN compendia and addition of combination options (for example, combinations with daratumumab/Darzalex Faspro, carfilzomib/Kyprolis and dexamethasone, and other NCCN‑recommended regimens).
References supporting clinical use: Xpovio (selinexor) prescribing information and NCCN Drugs & Biologics Compendium and disease‑specific NCCN guidelines (Multiple Myeloma; B‑Cell Lymphomas) are cited and were reviewed/updated in policy history.

Initial Therapy Criteria

inv-19: Initial Therapy — initial approval criteria by diagnosis.

Initial selinexor - MM: See 'Initial Therapy - Multiple Myeloma' criteria: diagnosis, prescriber specialty, age ≥ 18, use of selinexor if available, relapsed/refractory disease, required concomitant regimens or prior therapy history, and regimen-specific dose limits (100 mg/week with bortezomib+dexamethasone; 160 mg/week other combos).

Prior authorization may be required for listed concomitant agents; prescriber must provide supporting documentation for off-label dosing.

Initial selinexor - B-cell lymphoma: See 'Initial Therapy - B-cell Lymphoma' criteria: eligible diagnoses, prescriber specialty, age ≥ 18, use of selinexor if available, relapsed/refractory disease, ≥ 2 prior therapies, and dose limit of 120 mg/week (6 tablets/week) unless supported by guidelines/literature).

Prescribed regimen must be FDA-approved or recommended by NCCN; prior authorization may be required.

inv-20: Initial therapy considerations — policy history notes and dosing availability changes relevant at initiation.

Product availability at initiation: Tablets available in multiple strengths including 10 mg and 80 mg additions per RT4; prescribers should note newly available strengths when calculating tablet counts and weekly limits.

RT4 revisions added 10 mg and 80 mg strengths and aligned B-cell lymphoma maximum dosing criteria to 120 mg/week.

Continuation Therapy Criteria

inv-21: Continuation Therapy — criteria for continued therapy.

Continued selinexor use: 1) Member has documented at least 30 days current use for a covered indication or is currently receiving medication via the Centene benefit; 2) Member demonstrates clinical benefit or is responding to therapy; 3) Member must use selinexor if available unless contraindicated; 4) Ongoing dosing must remain within policy weekly limits (MM: 100 mg/week with bortezomib regimen or 160 mg/week other combos; B-cell lymphoma: 120 mg/week) or be justified by guidelines/literature for off-label dosing; 5) Requests for dose increases require supporting documentation if exceeding standard limits.

Approval durations specified by line of business (Medicaid/HIM - 12 months; Commercial - 12 months or duration requested, whichever is less).

inv-22: Continuation therapy duration — administrative revision affecting continuation/approval durations for maintenance therapy in Medicaid/HIM lines.

Medicaid/HIM maintenance approval duration: Initial approval duration extended from 6 months to 12 months for this maintenance medication for a chronic condition.

Administrative RT4 revision effective 01.28.26 added 80 mg strength and extended Medicaid/HIM initial approval durations to 12 months.

Step Therapy and Therapeutic Alternatives

Combination / Context	Step therapy implication / requirement
Selinexor prescribed in combination with bortezomib and dexamethasone (MM)
Requires dose not to exceed 100 mg per week (5 tablets per week); prior authorization may be required for listed agents (see Appendix B for therapeutic alternatives).
Selinexor prescribed in combination regimens other than bortezomib+dexamethasone (MM) (e.g., daratumumab + dexamethasone; carfilzomib + dexamethasone; pomalidomide + dexamethasone)
Requires dose not to exceed 160 mg per week (8 tablets per week) unless supported by practice guidelines or peer‑reviewed literature; prior authorization may be required for concomitant agents and Appendix B lists therapeutic alternatives.
Selinexor with dexamethasone for heavily pretreated MM (≥4 prior therapies including 2 proteasome inhibitors, 2 immunomodulatory agents, and 1 anti‑CD38 antibody)
Treated as combination regimen per policy with the same dose limits as applicable above; prior authorization may be required and regimens should be FDA‑approved or recommended by NCCN (see Appendix B for alternatives).
Selinexor for B‑cell lymphomas/DLBCL (monotherapy or labeled combinations per NCCN)
Dose limit 120 mg per week (6 tablets); regimens must be FDA‑approved or NCCN‑recommended and prior authorization may be required.

Update / Revision	Impact on step therapy pathways
RT4 and subsequent policy revisions added combination regimen options aligned with NCCN recommendations (examples: combinations including daratumumab, carfilzomib, etc.).
Inclusion of NCCN‑recommended combinations may alter prior step therapy sequencing and authorization requirements; these combinations are recognized as allowable regimens when criteria are met and may require prior authorization for concomitant agents per Appendix B.
Administrative changes (RT4) also added new tablet strengths (10 mg) and aligned B‑cell lymphoma maximum weekly dosing to 120 mg/week, supporting updated step therapy dosing rules.
Providers should document regimen selection and evidence when doses exceed regimen‑specific limits; policy continues to permit guideline‑supported exceptions which may affect step therapy failures or exemptions.

Quantity Limits

selinexor (Xpovio) — weekly limits

Maximum weekly tablet counts (by regimen)Bortezomib + dexamethasone: 5 tablets/week; all other MM combinations: 8 tablets/week; B‑cell lymphoma: 6 tablets/week

Maximum weekly mg (by regimen)100 mg/week with bortezomib regimen; 160 mg/week for other MM combinations; 120 mg/week for B‑cell lymphoma

Common MM dosing example80 mg PO on Days 1 and 3 weekly (combination with dexamethasone)

DLBCL dosing example60 mg PO on Days 1 and 3 weekly (documented DLBCL regimen)

Background

Selinexor (Xpovio) is an oral selective inhibitor of nuclear export (XPO1 inhibitor) indicated in combination regimens for multiple myeloma and as monotherapy with dexamethasone for certain relapsed/refractory B‑cell lymphomas. The agent received accelerated approval for relapsed/refractory diffuse large B‑cell lymphoma (DLBCL) after at least two prior systemic therapies based on response rate; full prescribing information and guideline references (NCCN) are cited in the policy for clinical context and dosing guidance.

Definitions and References

Acronyms

DLBCLDiffuse large B-cell lymphoma

MMMultiple myeloma

NOSNot otherwise specified

Prescribing information

Xpovio Prescribing InformationXpovio Prescribing Information. Karyopharm Therapeutics, Inc.; October 2025. Available at: https://www.xpovio.com. Accessed January 28, 2026.

Use in requestsProviders should reference the product labeling when submitting dosing or safety justification for doses outside policy limits

Clinical guideline references

NCCN Drugs & Biologics CompendiumNational Comprehensive Cancer Network Drugs and Biologics Compendium (accessed January 28, 2026)

NCCN Multiple Myeloma guidelineNCCN Multiple Myeloma Version 2.2025 (Accessed May 13, 2025)

NCCN B‑Cell Lymphomas guidelineNCCN B-Cell Lymphomas Version 2.2025 (Accessed May 13, 2025)

Site of Care

Note

Site‑of‑care — follow Health Plan guidance; no mandated site

Standard site‑of‑care guidance applies based on the member's Health Plan; the policy does not mandate a specific site and does not require home administration.

Site‑of‑care decisions follow Health Plan policies and contracts; this clinical policy is a coverage guide and does not dictate site‑of‑care.