CurrentUnitedHealthcarePolicy 2025 P 1296-6

Xpovio (selinexor) prior authorization/notification policy

Defines UnitedHealthcare prior authorization and reauthorization clinical criteria for Xpovio (selinexor) for multiple myeloma and relapsed/refractory diffuse large B-cell lymphoma (DLBCL), including pediatric auto-approval rules and references to NCCN guidance and state mandates.

Policy Summary

PayerUnitedHealthcare

PolicyXpovio (selinexor) prior authorization/notification policy

Policy CodePolicy 2025 P 1296-6

Change TypeAnnual reviewreference and criteria updates

Effective DateApr 1, 2025

Next Review Date

Key ActionPrior authorization/notification is required and members must meet the stated clinical criteria for approval; authorization is issued for 12 months when criteria are met.

SourceLink

POLICY UPDATE CHANGES

Annual review; updated background and indicated formatting for consistency. Included coverage criteria for diffuse large B-cell lymphoma according to NCCN recommendations and updated references.

Added coverage criteria for DLBCL according to label.

2Major covered indications (MM, DLBCL)

12 moAuthorization duration

>=4Prior therapies threshold (RRMM refractory pathway)

<19Automatic approval age cutoff

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Summary

Scope: This policy defines UnitedHealthcare prior authorization and reauthorization clinical criteria for Xpovio (selinexor) for multiple myeloma (MM) and relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Coverage stance: covered with criteria. Major covered indications include Xpovio in combination regimens for MM (including combinations with bortezomib + dexamethasone, daratumumab + dexamethasone, carfilzomib + dexamethasone, or pomalidomide + dexamethasone per specific criteria) and for relapsed/refractory DLBCL (after at least 2 lines of systemic therapy). Pediatric processing: prescriptions for patients 19 years automatically process without a coverage review. Authorization duration when criteria are met is 12 months. NCCN guidance and applicable state mandates/compendia are referenced as high-level context and may supersede policy where required.

Thresholds and Authorization Parameters

Progression window after last therapy<= 60 days (patient has demonstrated progression on or within 60 days of completion of the last therapy)

Number of prior therapies - RRMM refractory category>= 4 prior therapies

Number of prior therapies - DLBCL>= 2 lines of systemic therapy

Number of prior therapies - NCCN MM combo with pomalidomide>= 2 prior therapies including an immunomodulatory agent and a proteasome inhibitor

Authorization duration12 months

Automatic approval age cutoff< 19 years

Initial Authorization — Multiple Myeloma (MM / RRMM)

Initial Authorization — Multiple Myeloma and Relapsed/Refractory Multiple Myeloma (RRMM)

Xpovio will be approved based on one of the following clinical scenarios:

ANY of the following

Scenario 1 — RRMM with heavy prior therapy
- Diagnosis of relapsed or refractory multiple myeloma (RRMM)
- Patient has received at least four prior therapies>=4 prior therapies
- Refractory to all of the following
  - Two proteasome inhibitors (e.g., bortezomib, carfilzomib)

Reauthorization — Multiple Myeloma

Criteria to approve continued therapy:

ALL of the following

Patient does not show evidence of progressive disease while on Xpovio therapy

Initial Authorization — DLBCL and Related Lymphomas

Initial Authorization — DLBCL and related lymphomas

Xpovio will be approved based on both of the following:

ALL of the following

Eligible diagnoses (one of)
- Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including histologic transformation of indolent lymphomas to DLBCL
- Relapsed or refractory HIV-related diffuse large B-cell lymphoma
- Primary effusion lymphoma
- HHV8-positive diffuse large B-cell lymphoma

Reauthorization — DLBCL and Related Lymphomas

Reauthorization — DLBCL and related lymphomas

Criteria to approve continued therapy:

ALL of the following

Patient does not show evidence of progressive disease while on Xpovio therapy

Provider Actions

Prior Authorization

Prior authorization required for Xpovio

Prior authorization/notification is required and members must meet the stated clinical criteria for approval; authorization is issued for 12 months when criteria are met.

Documentation Required

Documentation of prior therapies and refractoriness

Providers must document prior lines of therapy and list the specific agents received (for example, proteasome inhibitors, immunomodulatory agents, anti‑CD38 antibody) and provide evidence of refractory disease or progression as specified in the clinical criteria.

Applicable Codes & Diagnosis Examples

Referenced diagnosis examples (non-exhaustive, policy references ICD-10 codes for automated approvals)ICD-10

C90.0	Multiple myeloma
C85.1	Diffuse large B-cell lymphoma
C83.7	Primary effusion lymphoma
C88.4	HHV8-positive diffuse large B-cell lymphoma (histologic transformation/related entities)
C85.2	Post-transplant lymphoproliferative disorder, monomorphic B-cell type

Clinical Evidence & References

Evidence summary: P&T approval date for the program is 10/2019. The package insert reference is Xpovio [package insert], Karyopharm Therapeutics Inc; July 2022. FDA indications noted in the background include Xpovio in combination with bortezomib and dexamethasone for adults with MM after at least one prior therapy, Xpovio plus dexamethasone for adults with relapsed or refractory MM after at least 4 therapies with specified refractory classes, and Xpovio for relapsed/refractory DLBCL after at least 2 lines of systemic therapy. NCCN recognition: the drug is recognized in the NCCN Drugs & Biologics Compendium with Categories of Evidence and Consensus of 1, 2A, or 2B for certain cancer indications and NCCN also recommends listed combination regimens for previously treated MM and for DLBCL as described.

Definitions

Refractory: Disease not responding to or progressing despite therapy; the policy requires refractory status to specified classes where noted (for example, RRMM refractory to two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody in the heavily pretreated pathway).

Line(s) of therapy: Prior systemic treatments given for the cancer indication; specific numeric thresholds are required per criteria (examples in this policy include ≥4 prior therapies for the RRMM refractory pathway, ≥2 prior therapies for DLBCL, and ≥1 prior therapy for the MM indication when used with bortezomib + dexamethasone).

Revision History

2025-01-01annual_reviewLatest

Annual review; updated background and indicated formatting for consistency. Included coverage criteria for diffuse large B-cell lymphoma according to NCCN recommendations and updated references. (Listed in change control history for 1/2025; latest entry indicates reference updates.)

2022-01-01criteria_added

Added coverage criteria for DLBCL according to label. (Change recorded 1/2022 and reiterated in subsequent reviews.)

Policy Summary

PayerUnitedHealthcare

PolicyXpovio (selinexor) prior authorization/notification policy

Policy CodePolicy 2025 P 1296-6

Change TypeAnnual reviewreference and criteria updates

Effective DateApr 1, 2025

Next Review Date

Key ActionPrior authorization/notification is required and members must meet the stated clinical criteria for approval; authorization is issued for 12 months when criteria are met.

SourceLink

On This Page

Two immunomodulatory agents (e.g., lenalidomide, thalidomide)

An anti-CD38 monoclonal antibody (e.g., daratumumab)

Used in combination with dexamethasone

Scenario 2 — Multiple myeloma after ≥1 prior therapy (label indication)

Diagnosis of multiple myeloma
Patient has received at least one prior therapy>=1 prior therapy
Required combination regimens
- Velcade (bortezomib) and dexamethasone
- Darzalex (daratumumab) and dexamethasone
- Kyprolis (carfilzomib) and dexamethasone

Scenario 3 — NCCN-recommended combination with pomalidomide

Diagnosis of multiple myeloma
Patient has received at least 2 prior therapies, including an immunomodulatory agent (e.g., lenalidomide, thalidomide) and a proteasome inhibitor (e.g., bortezomib, carfilzomib)>=2 prior therapies including an IMiD and a PI
Patient has demonstrated progression on or within 60 days of completion of the last therapy<= 60 days
Used in combination with Pomalyst (pomalidomide) and dexamethasone

Relapsed or refractory monomorphic B-cell type post-transplant lymphoproliferative disorder

Patient has received at least 2 lines of systemic therapy>=2 lines of systemic therapy

Billing Rule

Automatic processing for patients <19 years

For members under the age of 19 years, the prescription will automatically process without a coverage review.

Billing Rule

Automated approval processes may be used

UnitedHealthcare may use automated approval and reauthorization processes based solely on prior claim/medication history, diagnosis codes (ICD‑10), and claim logic; supply limits may apply.

Documentation Required

State mandates and compendia

Comply with applicable state mandates for off‑label coverage and use of compendia; where state mandates or compendia requirements apply, they supersede the policy language.

Denial Risk

Reauthorization denial if progression

Reauthorization may be denied if the patient shows evidence of progressive disease while on Xpovio therapy.