CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Um Onc_1224 Kyprolis Carfilzomib_11292024

Defines accepted indications, continuation and exclusion criteria, and utilization management authority for Kyprolis (carfilzomib) including FDA-approved and supported off-label uses per CMS-recognized compendia and guideline sources. Specifies permitted regimens for relapsed/refractory multiple myeloma and notes regimens not supported for newly diagnosed disease.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyUm Onc_1224 Kyprolis Carfilzomib_11292024

Policy CodePolicy N/A

Change TypeNo material change

Effective DateNov 29, 2024

Next Review Date

Key ActionRequests must be supported by FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or peer-reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15 requirements.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this policy update.

Relapsed/RR MMCovered Indication (conditional)

Newly dx, TINot supported (KRd)

Newly dx, TENot supported (Daratumumab+Kyprolis+Rd)

Dose limitsDosing constraints

This policy defines the accepted indications and utilization management for Kyprolis (carfilzomib). It takes a mixed coverage stance: Kyprolis is conditionally covered for relapsed or refractory multiple myeloma after 1–3 prior therapies when used in specified combinations, but certain Kyprolis‑based regimens for newly diagnosed disease are not supported. The policy relies on FDA labeling and CMS‑recognized compendia and guideline sources (NCCN, ASCO) and peer‑reviewed literature to determine acceptable uses. Evolent reviews and processes medication requests and may deem medications not authorized under this policy as not approvable and therefore not reimbursable.

Policy metadata & thresholds

Effective dateNovember 29, 2024

Last reviewNovember 13, 2024

StatusCURRENT

SubjectKyprolis (carfilzomib) coverage and utilization policy

Single dose limit56 mg/m2 twice weekly OR 70 mg/m2 once weekly

Initial Therapy — Covered Regimens (Relapsed/Refractory MM)

Covered Use in Multiple Myeloma (Relapsed/Refractory)

For relapsed or refractory multiple myeloma after 1-3 prior therapies, Kyprolis (carfilzomib) may be used when ANY ONE of the following regimen options is requested:

ANY of the following

Regimen: dexamethasone: In combination with dexamethasone
Regimen: lenalidomide +/- steroid: In combination with lenalidomide +/- steroid
Regimen: cyclophosphamide +/- steroid: In combination with cyclophosphamide +/- steroid
Regimen: daratumumab +/- steroid: In combination with daratumumab +/- steroid
Regimen: pomalidomide +/- steroid: In combination with pomalidomide +/- steroid

Continuation Therapy Criteria

Continuation requests for a not-approvable medication shall be exempt from this Evolent policy provided ALL of the following are met:

Continuation Requests Exemption

The requested medication was used within the last year.
The member has not experienced disease progression and/or intolerance to the requested medication.
No additional medication(s) are being added to the continuation request.

Prior Authorization

Continuation exemption documentation

For continuation requests that meet the exemption above, the provider must document prior use and the absence of progression/intolerance, and must confirm no new medications are being added. Additionally, for any off‑label or investigational use of carfilzomib, submit supporting evidence from FDA labeling, CMS‑recognized compendia, NCCN/ASCO guidelines, or adequate peer‑reviewed literature addressing: patient population similarity, regimen representation, clinically meaningful outcomes, and study design adequacy per CMS Medicare Benefit Policy Manual Chapter 15. Inadequate evidence (case reports, abstracts without full articles, or unsupported investigational uses) may result in denial.

Document prior use of the requested medication within the last 12 months.
Document that the member has not had disease progression or intolerance to the medication.
Confirm and document that no additional medications are being added to the continuation request.
For investigational/off‑label requests, include citations to FDA label, CMS compendia, NCCN or ASCO guidance, or peer‑reviewed studies that adequately represent the patient population, regimen, and clinically meaningful outcomes.
Notes on unacceptable evidence types: case reports, meeting abstracts without full articles, or other anecdotal reports are insufficient.

Exclusions and Not Approvable Conditions

Exclusion Criteria

Kyprolis is NOT approvable when ANY of the following exclusion criteria are met:

ANY of the following

Progression on therapy: Member has disease progression while taking Kyprolis (carfilzomib)
Dosing exceeds single dose limit of Kyprolis (carfilzomib) 56 mg/m2 twice weekly or 70 mg/m2 once weeklysingle dose limit: 56 mg/m2 twice weekly OR 70 mg/m2 once weekly
Investigational/off-label insufficient evidence: Investigational use of Kyprolis (carfilzomib) with an off-label indication that is not sufficient in evidence or is not generally accepted by the medical community
Sufficient evidence is defined by criteria referencing CMS compendia, peer-reviewed literature, study representativeness, clinically meaningful outcomes, appropriate design, and adequate subject numbers; excludes isolated case reports and abstracts without full articles

Denial Risk

Denial risk — dosing limits enforced

Claims will be excluded/not approvable if the single dose exceeds the policy limits: 56 mg/m2 when given twice weekly, or 70 mg/m2 when given once weekly.

Not Supported / Not Recommended Regimens in Multiple Myeloma (Newly Diagnosed)

Evolent does NOT support the following Kyprolis-based regimens in newly diagnosed multiple myeloma:

Not supported regimens (newly diagnosed)

KRd not supported - transplant ineligible: Kyprolis-based regimens (e.g., KRd) for newly diagnosed, transplant ineligible multiple myeloma are not supported by Evolent Policy
NOTE 1: Position based on ENDURANCE trial showing equivalent outcomes and increased cardiotoxicity compared to bortezomib-based regimen
Daratumumab + Kyprolis + Rd not supported - transplant eligible: Daratumumab + Kyprolis (carfilzomib) + Revlimid (lenalidomide) + Dexamethasone is not supported by Evolent Policy for newly diagnosed, transplant eligible multiple myeloma
NOTE 2: Position based on lack of Level 1 evidence of superiority compared to daratumumab + bortezomib + lenalidomide + dexamethasone

Documentation Required

Documentation — evidence required for off‑label indications

For off‑label or investigational uses, provide literature that demonstrates sufficient evidence per policy: the patient and cancer match populations represented in the published evidence; the exact regimen is represented; reported outcomes are clinically meaningful (ASCO‑recommended thresholds, e.g., hazard ratio < 0.80 and OS/PFS benefit ≥ 3 months); study design is appropriate to the question; and subject numbers are adequate. Note that isolated case reports and meeting abstracts without full peer‑reviewed articles are generally insufficient.

Provider Actions & Prior Authorization Requirements

Prior Authorization

Supporting evidence required for authorization

Authorization requests must be supported by one of the following: FDA‑approved product labeling, CMS‑recognized compendia, NCCN or ASCO clinical guidelines, or peer‑reviewed literature that meets the requirements of the CMS Medicare Benefit Policy Manual Chapter 15.

Documentation Required

What to include on prior authorization forms for continuation

On prior authorization forms, explicitly state that the medication was used within the past year, attest that the member has not had disease progression and/or has not had intolerance to the medication while on it, and confirm that no additional medication(s) are being added to the continuation request.

Clinical Evidence & Trials

Key supporting trials and findings cited in the policy include:

- ENDURANCE: a phase 3 randomized trial comparing carfilzomib+lenalidomide+dexamethasone to bortezomib+lenalidomide+dexamethasone that found equivalent outcomes but increased cardiotoxicity with the carfilzomib regimen.

- ENDEAVOR: a randomized phase 3 trial comparing carfilzomib+dexamethasone versus bortezomib+dexamethasone in relapsed/refractory multiple myeloma (used as evidence supporting Kyprolis regimens in the relapsed setting).

- CANDOR: a randomized phase 3 study reporting updated outcomes for carfilzomib+dexamethasone+daratumumab versus carfilzomib+dexamethasone in relapsed/refractory multiple myeloma.

Evidence highlights

ENDURANCE trialFound equivalent outcomes and increased cardiotoxicity for carfilzomib+lenalidomide+dexamethasone vs bortezomib+lenalidomide+dexamethasone

ENDEAVOR trialCarfilzomib+dexamethasone vs bortezomib+dexamethasone in relapsed/refractory MM

CANDOR trialCarfilzomib+dexamethasone+daratumumab vs carfilzomib+dexamethasone updated outcomes

Definitions & Background

Policy determinations are based on: FDA‑approved product labeling and the Kyprolis prescribing information; CMS‑recognized compendia and the CMS Medicare Benefit Policy Manual Chapter 15 evidence standards; NCCN and ASCO clinical guidelines; and peer‑reviewed literature. The policy specifies documentation and evidence expectations for authorization, enforces dosing limits, and grants Evolent authority to process requests and deem medications not authorized under the policy as not approvable.

Definitions

Sufficient evidence (definition)Evidence supported by CMS compendia or acceptable peer-reviewed literature addressing representativeness, regimen, clinically meaningful outcomes (e.g., HR <0.80, OS/PFS benefit ≥3 months), appropriate design, and adequate subject numbers; excludes isolated case reports and abstracts without full articles.