CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Xpovio (selinexor) — Coverage Criteria for Hematologic Malignancies

Defines clinical indications, limits, and documentation/coding guidance for authorization of Xpovio (selinexor) for members of Neighborhood Health Plan of Rhode Island processed by Evolent; applies to providers submitting medication requests.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyXpovio (selinexor) — Coverage Criteria for Hematologic Malignancies

Policy CodePolicy N/A

Change TypeUpdated exclusionstemplate conversion

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization for selinexor (J8999) and document clinical criteria per policy for DLBCL or multiple myeloma.

SourceLink

POLICY UPDATE CHANGES

Updated exclusion criteria.

Converted to new Evolent guideline template and replaced prior UM ONC_1365 Xpovio (selinexor) policy.

2Indications described

60 mg / 100 mgSingle dose maximums

32/16/8/4Monthly tablet limits

J8999Billing code

Coverage Criteria for Xpovio (selinexor)

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Diffuse Large B-Cell Lymphoma (DLBCL)

Covered when ALL of the following are met for relapsed/refractory DLBCL:

DLBCL coverage criteria: Member has relapsed/refractory diffuse large B-cell lymphoma.

DLBCL lines of therapy: Documented disease progression on 2 or more prior lines of therapy.>=2 prior lines

Transplant status: Either failed autologous stem-cell transplant or was not eligible/suitable for autologous stem-cell transplant based on clinical assessment.

Single-agent selinexor use for DLBCL per policy.

Multiple Myeloma (MM)

Covered when ANY of the following regimen-specific criteria are met for relapsed/refractory multiple myeloma:

MM - quadruple-class exposed (selinexor + dexamethasone): Member has relapsed/refractory multiple myeloma with documented disease progression on at least 4 prior lines of therapy including two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody; selinexor used in combination with dexamethasone (unless contraindicated).>=4 prior lines including specified classes

Selinexor + dexamethasone pathway; corresponds to class-exhausted patients.

MM - earlier line bortezomib combination: Member has relapsed/refractory multiple myeloma and is receiving selinexor in combination with bortezomib with or without dexamethasone after one prior therapy.>=1 prior therapy

Allows selinexor + bortezomib +/- dexamethasone for earlier relapse setting.

Coverage is excluded when there is documented disease progression while receiving Xpovio (selinexor). Requests will also be excluded if dosing exceeds the policy single-dose limits: 60 mg for diffuse large B‑cell lymphoma (DLBCL) or 100 mg for multiple myeloma (MM). Additionally, treatment that would exceed the monthly tablet maximums is excluded: 32 tablets of 20 mg, 16 tablets of 40 mg, 8 tablets of 50 mg, or 4 tablets of 60 mg per month. Use of selinexor for investigational or off‑label indications that lack sufficient supporting evidence as defined by the policy is also excluded.

Selinexor given in combination with daratumumab, with or without dexamethasone, for relapsed/refractory multiple myeloma is not supported by this policy. This position is based on the lack of Level 1 evidence (randomized clinical trials and/or meta-analyses) demonstrating superior outcomes with the selinexor + daratumumab ± dexamethasone regimen compared with Evolent‑recommended alternative therapies; therefore the regimen is considered not medically necessary under this guideline.

Covered Regimens and Indication-Specific Use

Regimen	Indication	Coverage
Selinexor (single agent)
Relapsed/refractory diffuse large B-cell lymphoma with documented disease progression on ≥2 prior lines of therapy AND failed autologous stem-cell transplant or not eligible/suitable for autologous stem-cell transplant based on clinical assessment.
Covered when all criteria above are met.

Regimen	Indication	Coverage
Selinexor + Dexamethasone
Relapsed/refractory multiple myeloma with documented disease progression on ≥4 prior lines of therapy including two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody; dexamethasone used unless contraindicated or intolerant.
Covered when criteria above are met (reserved for heavily pretreated/quadruple-class exposed patients).

Regimen	Indication	Coverage
Selinexor + Bortezomib ± Dexamethasone
Relapsed/refractory multiple myeloma in members who have received one prior therapy.
Covered when used after one prior therapy as specified.

Regimen	Indication	Coverage
Selinexor + Daratumumab ± Dexamethasone
Relapsed/refractory multiple myeloma (combination with daratumumab as listed).
Not covered — not supported by policy due to lack of Level 1 evidence.

Line-of-Therapy Requirements

salvage — line-of-therapy

Salvage - line-of-therapy requirement: Documented progression on 2 or more prior lines of therapy (salvage setting).>=2 prior lines

Applies to DLBCL salvage therapy pathway; also requires transplant failure or ineligibility as applicable.

first-line — line-of-therapy

First-line (MM) - quadruple-class exposed pathway: Progression on at least 4 prior lines including two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody (selinexor + dexamethasone pathway).>=4 prior lines

Reserved for heavily pretreated MM as specified.

First-line (MM) - one prior therapy pathway: One prior therapy received (selinexor in combination with bortezomib +/- dexamethasone).>=1 prior line

Allows selinexor + bortezomib +/- dexamethasone after one prior therapy.

Provider Actions, Authorization & Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for selinexor (HCPCS J8999). Coverage will be granted only when clinical criteria in the policy are met. Providers must submit a prior authorization request to Evolent (on behalf of Neighborhood Health Plan of Rhode Island) with supporting documentation as described below.

Affected code: J8999 (selinexor)

Documentation Required

Continuation Therapy — Submission Requirements

Continuation requests for members already receiving selinexor may be approved without re‑meeting all initial criteria only when the continuation conditions below are met. Do not submit a continuation request if disease progression has occurred on selinexor.

Continuation eligible when: member has not experienced disease progression on selinexor; therapy was used within the last 12 months with no lapse >30 days from an active authorization; and no additional medications are being added to the continuation request.
Requests for continued coverage must include documentation of clinical benefit (e.g., radiographic reports, laboratory markers, clinician progress notes) and current dosing details.

Denial Risk

Denial Triggers / Exclusion Conditions

Selinexor requests may be denied for any of the exclusion conditions below. Review these denial triggers carefully before submitting an authorization request; missing or conflicting documentation that indicates an exclusion condition may result in denial.

Disease progression while receiving Xpovio (selinexor).
Dosing that exceeds single‑dose limits: >60 mg single dose for DLBCL or >100 mg single dose for multiple myeloma.
Treatment that exceeds monthly tablet limits: more than 32 tablets of 20 mg, 16 tablets of 40 mg, 8 tablets of 50 mg, or 4 tablets of 60 mg per month.
Requests for investigational or off‑label indications that lack sufficient supporting evidence (not supported by FDA labeling, CMS‑recognized compendia, NCCN/ASCO guidelines, or acceptable peer‑reviewed literature).
Insufficient evidence when published literature does not adequately represent the patient/cancer population, the administered regimen, or clinically meaningful outcomes (per ASCO criteria, e.g., HR <0.80 or survival benefit thresholds).
Reliance on case reports or meeting abstracts without full peer‑reviewed articles as primary support for an off‑label use.

Definitions and Accepted Evidence Sources

Sufficient supporting evidence — FDA label, CMS compendia, NCCN/ASCO, or acceptable peer-reviewed literature

Accepted evidence sourcesFDA-approved product labeling, CMS-recognized compendia, NCCN or ASCO clinical guidelines, or peer-reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15

Peer-reviewed literature standardsEvidence should represent the patient population/regimen, report clinically meaningful outcomes (ASCO definitions: e.g., HR <0.80, OS/PFS benefit ≈≥3 months), and use appropriate study design

Unacceptable evidence typesCase reports and meeting abstracts without full peer-reviewed publication generally lack adequate supportive evidence

Investigational/off-label determinationOff-label uses lacking support from CMS compendia or acceptable peer-reviewed literature are considered investigational and excluded

Background

Xpovio (selinexor) is an oral selective inhibitor of nuclear export used in certain relapsed/refractory hematologic malignancies. The policy frames selinexor coverage around specific, indication‑based criteria and limits: single‑agent selinexor is addressed for relapsed/refractory DLBCL after prior therapies and transplant failure or ineligibility, and combination regimens (for example with dexamethasone or bortezomib) are permitted for defined multiple myeloma scenarios. The policy also establishes explicit dosing controls and exclusion conditions (including progression on selinexor, single‑dose ceilings, monthly tablet maximums, and investigational/off‑label use lacking sufficient evidence) to guide authorization decisions.