CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Ninlaro (ixazomib) coverage criteria

Defines accepted indications, coverage conditions, and exclusions for ixazomib (Ninlaro) for Neighborhood Health Plan of Rhode Island members; applies to providers submitting medication requests processed by Evolent.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyNinlaro (ixazomib) coverage criteria

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

Key ActionSubmit prior authorization to Evolent with supporting FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

J8999HCPCS code listed for ixazomib

Commercial, Exchange, MedicaidLines of business

Max 4 mgPer-dose limit

Max 3/monthMonthly capsule limit

≤30-day lapseContinuation rule

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General coverage criteria

Covered only when ALL of the following are met (and not excluded):

Supportive documentation: Use must be supported by FDA approved product labeling, CMS-recognized compendia, NCCN or ASCO clinical guidelines, or acceptable peer-reviewed literature that meets CMS standards.

See Purpose and References.

Continuation criteria: For continuation requests: member has not experienced disease progression on ixazomib, prior use within the last year without >30-day lapse, and no additional medications are being added.

Continuation exemptions per policy.

Dosing limits: Single dose must not exceed 4 mg and total treatment must not exceed 3 capsules per month (available capsule strengths 4 mg, 3 mg, 2.3 mg).single dose ≤ 4 mg; ≤3 capsules/month

Exceeding these limits is exclusionary.

Multiple myeloma — not supported

Not supported for multiple myeloma

Multiple myeloma stance: Ixazomib (Ninlaro) and ixazomib-containing regimens are not supported for treatment of multiple myeloma due to lack of Level 1 evidence demonstrating superiority over bortezomib in the first-line setting or over carfilzomib in the relapsed/refractory setting.

For patients with failure/intolerance/contraindication to bortezomib in first-line, carfilzomib-based regimens would be supported per Evolent policy; refer to Evolent Pathways for alternative regimens.

Coverage will be denied when any of the following exclusionary conditions are met: disease progression on Ninlaro (ixazomib) or an ixazomib-containing regimen; dosing that exceeds the single-dose limit of 4 mg; or treatment that exceeds the maximum of 3 capsules per month (capsule strengths: 4 mg, 3 mg, 2.3 mg). Requests for investigational or off‑label indications lacking sufficient supporting evidence (per the policy’s evidence standards) are also exclusionary.

Use of Ninlaro (ixazomib) for indications that are investigational or off‑label is not approvable unless supported by FDA labeling, CMS‑recognized compendia, NCCN/ASCO guidelines, or acceptable peer‑reviewed literature meeting the policy’s evidence standards. Specifically, the policy does not support ixazomib for multiple myeloma because there is a lack of Level 1 evidence showing superiority over bortezomib in first‑line disease or over carfilzomib in the relapsed/refractory setting; alternative agents and regimens recommended by Evolent should be considered.

Regimen example	Indication / coverage stance
Ixazomib + lenalidomide + dexamethasone	Multiple myeloma — not supported by policy due to lack of Level 1 evidence showing superiority over bortezomib (first‑line) or carfilzomib (relapsed/refractory).
Other ixazomib‑containing regimens (oral ixazomib combined with standard anti‑myeloma agents)	Multiple myeloma — not supported by policy for first‑line or relapsed/refractory treatment; alternatives (e.g., bortezomib or carfilzomib‑based regimens) recommended per Evolent pathways and policy guidance.

Actions required of ordering providers

Prior Authorization

Prior Authorization Required

Prior authorization required. Evolent processes all medication requests from network ordering providers; medications not authorized by Evolent may be deemed not approvable and not reimbursable.

Evolent is responsible for processing all medication requests from network ordering providers.
Medications not authorized by Evolent may be deemed as not approvable and therefore not reimbursable.

Step Therapy

Therapy Preference / Step Guidance

Ninlaro (ixazomib) and Ninlaro-containing regimens are not supported by the Evolent Ninlaro Policy for the treatment of multiple myeloma. For members with failure/intolerance/contraindication to Velcade (bortezomib) in the first-line setting, carfilzomib (Kyprolis) is supported per Evolent policy. Refer to alternative agents/regimens recommended by Evolent (e.g., Evolent Pathways).

Policy preference against ixazomib for multiple myeloma in both first-line and relapsed/refractory settings due to lack of Level 1 evidence.
Support alternative agents (e.g., bortezomib or carfilzomib) per Evolent guidance.

Documentation Required

Required Supporting Documentation

Support for use must be documented by FDA labeling, CMS‑approved compendia, NCCN or ASCO clinical guidelines, or peer‑reviewed literature that meets CMS standards.

Acceptable evidence sources: FDA approved product labeling; CMS‑recognized compendia; NCCN or ASCO clinical guidelines; peer‑reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15 requirements.
Investigational or off‑label indications require sufficient supporting evidence per CMS compendia or acceptable peer‑reviewed literature; abstracts, single case reports, or insufficient evidence are not acceptable.

Denial Risk

Continuation Rules and Denial Triggers

Continuation requests for a previously authorized medication may be exempt from reauthorization review only when conditions are met; otherwise prior authorization and exclusion criteria apply.

Continuation allowed if: member has not experienced disease progression on the requested medication; medication was used within the last year without a lapse of more than 30 days of active authorization; and no additional medications are being added to the continuation request.
Exclusion criteria that trigger denial include: disease progression on ixazomib or an ixazomib‑containing regimen; dosing exceeding single dose limit of 4 mg; treatment exceeding maximum of 3 capsules per month (4 mg/3 mg/2.3 mg); investigational use or off‑label indications without sufficient evidence or not generally accepted by the medical community.

Definitions and policy positions

Not supported for multiple myeloma

Policy stanceIxazomib (Ninlaro) and Ninlaro-containing regimens are not supported for treatment of multiple myeloma.

RationaleLack of Level 1 evidence (randomized trials and/or meta-analyses) demonstrating superior outcomes of ixazomib‑based regimens versus bortezomib (first-line) or carfilzomib (relapsed/refractory).

ImplicationFor first-line patients who fail/intolerant/contraindicated to bortezomib, carfilzomib (Kyprolis) would be supported per Evolent policy; refer to Evolent Pathways for alternative regimens.

Related exclusionsRequests will be excluded/denied for disease progression on ixazomib or ixazomib-containing regimens and for investigational/off‑label uses lacking sufficient evidence (per policy criteria).

Background on ixazomib

Ixazomib (Ninlaro) is an oral proteasome inhibitor used in certain multiple myeloma regimens. This policy restricts its use because available evidence does not demonstrate superiority of ixazomib‑based regimens versus established proteasome inhibitors (bortezomib first‑line; carfilzomib in relapsed/refractory disease). As a result, the policy limits coverage to situations supported by recognized compendia, guidelines, or adequate peer‑reviewed evidence and excludes use when disease progression has occurred on ixazomib, dosing limits are exceeded, or evidence for the requested off‑label indication is insufficient.

OpenPayer

Ninlaro (ixazomib) coverage criteria

Coverage criteria for ixazomib (Ninlaro)

Ixazomib-containing regimens

Billing and coding

Actions required of ordering providers

Line of therapy specifications

Definitions and policy positions

Background on ixazomib