CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Kyprolis (carfilzomib) — Coverage Criteria for Multiple Myeloma and Related Uses

Defines accepted indications, coverage criteria, exclusions, and coding for Kyprolis (carfilzomib) for treatment of multiple myeloma and other cancer uses; applies to providers submitting medication requests processed by Evolent for Neighborhood Health Plan of Rhode Island lines of business.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyKyprolis (carfilzomib) — Coverage Criteria for Multiple Myeloma and Related Uses

Policy CodePolicy N/A

Change TypeRoutine review — no material changes

Effective DateN/A

Next Review DateN/A

Key ActionSubmit prior authorization to Evolent with supporting FDA labeling or CMS-recognized compendia; continuation requests allowed if no disease progression and no >30-day lapse.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

J9047HCPCS code

1-3Allowed prior lines

56 mg/m2 / 70 mg/m2Single-dose limit

Commercial, Exchange, MedicaidLines of business

Coverage Criteria for Kyprolis (carfilzomib)

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyKyprolis (carfilzomib) — Coverage Criteria for Multiple Myeloma and Related Uses

Policy CodePolicy N/A

Change TypeRoutine review — no material changes

Effective DateN/A

Next Review DateN/A

Key ActionSubmit prior authorization to Evolent with supporting FDA labeling or CMS-recognized compendia; continuation requests allowed if no disease progression and no >30-day lapse.

SourceLink

On This Page

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Coverage criteria for multiple myeloma

Kyprolis (carfilzomib) coverage positions for multiple myeloma:

Relapsed/Refractory MM

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

Newly diagnosed — transplant ineligible: Kyprolis-based regimens (e.g., KRd) are not supported for newly diagnosed, transplant ineligible multiple myeloma based on the ENDURANCE trial which showed equivalent outcomes and increased cardiotoxicity compared with bortezomib-based regimens.

Newly diagnosed — transplant eligible: Daratumumab + Kyprolis + lenalidomide + dexamethasone is not supported for newly diagnosed, transplant eligible multiple myeloma due to lack of Level 1 evidence demonstrating superiority or lower toxicity compared to daratumumab + bortezomib + lenalidomide + dexamethasone.

Kyprolis‑based regimens are not supported for certain newly diagnosed multiple myeloma settings. Specifically, Evolent does not support Kyprolis (carfilzomib)‑based regimens (for example, KRd) for newly diagnosed, transplant‑ineligible patients based on the ENDURANCE trial showing equivalent outcomes and increased cardiotoxicity compared with a bortezomib‑based regimen. Likewise, daratumumab + Kyprolis + lenalidomide + dexamethasone is not supported for newly diagnosed, transplant‑eligible patients because Level 1 evidence demonstrating superior outcomes or lower toxicity versus the Evolent‑recommended daratumumab + bortezomib + lenalidomide + dexamethasone regimen is lacking. These positions are exclusions from coverage and providers should follow Evolent’s recommended alternative regimens (see Evolent Pathways).

Kyprolis-Based Regimens and Indications

Regimen	Indication	Coverage status	Notes
Kyprolis (carfilzomib)-based regimens (e.g., KRd)	Newly diagnosed, transplant ineligible multiple myeloma		Not supported by Evolent Policy based on ENDURANCE trial showing equivalent outcomes and increased cardiotoxicity compared with bortezomib-based regimen; Evolent recommends alternative regimens (see Evolent Pathways).

Regimen	Indication	Coverage status	Notes
Daratumumab + Kyprolis (carfilzomib) + lenalidomide + dexamethasone	Newly diagnosed, transplant eligible multiple myeloma		Not supported by Evolent Policy due to lack of Level 1 evidence demonstrating superiority or lower toxicity compared to daratumumab + bortezomib + lenalidomide + dexamethasone; Evolent recommends alternative regimens (see Evolent Pathways).

Regimen	Indication	Notes
Kyprolis (carfilzomib) in combination with dexamethasone	Relapsed or refractory multiple myeloma after 1-3 prior therapies	Allowed per policy as one of the permitted combination options for relapsed/refractory disease after 1-3 prior therapies.
Kyprolis (carfilzomib) in combination with lenalidomide +/- steroid	Relapsed or refractory multiple myeloma after 1-3 prior therapies	Allowed per policy as one of the permitted combination options for relapsed/refractory disease after 1-3 prior therapies.
Kyprolis (carfilzomib) in combination with cyclophosphamide +/- steroid	Relapsed or refractory multiple myeloma after 1-3 prior therapies	Allowed per policy as one of the permitted combination options for relapsed/refractory disease after 1-3 prior therapies.
Kyprolis (carfilzomib) in combination with daratumumab +/- steroid	Relapsed or refractory multiple myeloma after 1-3 prior therapies	Allowed per policy as one of the permitted combination options for relapsed/refractory disease after 1-3 prior therapies.
Kyprolis (carfilzomib) in combination with pomalidomide +/- steroid	Relapsed or refractory multiple myeloma after 1-3 prior therapies	Allowed per policy as one of the permitted combination options for relapsed/refractory disease after 1-3 prior therapies.

Permitted Lines of Therapy

second-line — relapsed/refractory multiple myeloma

ANY of the following

Kyprolis allowed in combination with dexamethasone
Kyprolis allowed in combination with lenalidomide +/- steroid
Kyprolis allowed in combination with cyclophosphamide +/- steroid
Kyprolis allowed in combination with daratumumab +/- steroid
Kyprolis allowed in combination with pomalidomide +/- steroid

Relapsed or refractory multiple myeloma (after 1-3 prior therapies) — quick facts

IndicationRelapsed or refractory multiple myeloma after 1-3 prior therapies

Allowed combinationsWith dexamethasone; with lenalidomide +/- steroid; with cyclophosphamide +/- steroid; with daratumumab +/- steroid; with pomalidomide +/- steroid

Line of therapySecond-line (after 1-3 prior therapies)

Not supported settingsNot supported for newly diagnosed transplant-ineligible or certain newly diagnosed transplant-eligible regimens per policy notes

Provider Requirements and Operational Rules

Prior Authorization

Prior Authorization Required

Prior authorization and continuation requests for Kyprolis (carfilzomib) are processed by Evolent on behalf of Neighborhood Health Plan of Rhode Island. Medications not authorized by Evolent may be deemed not approvable and not reimbursable. Providers must obtain prior authorization before initiating therapy unless an approved continuation exemption (see continuation conditions) applies.

Evolent processes all medication requests from network ordering providers.
Medications not authorized by Evolent may be deemed not approvable and not reimbursable.

Note

Continuation Request Conditions and Exemptions

Continuation requests for an existing authorization may be exempt from new prior authorization requirements when ALL of the following are met: the member has not experienced disease progression on the requested medication; the medication was used within the last year without a lapse of more than 30 days from an active authorization; and no additional medications are being added to the continuation request. If any of these conditions are not met, a full prior authorization review is required.

Exemption requires: no disease progression on the requested medication.
Exemption requires: medication used within last year with ≤30-day lapse from active authorization.
Exemption requires: no additional medications added to the continuation request.

Documentation Required

Supportive Documentation Required

Supportive documentation must accompany all requests. Acceptable sources to support use include FDA-approved product labeling, CMS-recognized compendia, NCCN or ASCO clinical guidelines, or peer-reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 standards. Requests lacking adequate supportive evidence or relying on insufficient peer-review (e.g., abstracts without full articles, single case reports) may be deemed investigational and excluded.

Acceptable documentation: FDA labeling, CMS-approved compendia, NCCN/ASCO guidelines, or qualifying peer-reviewed literature per CMS Chapter 15.
Insufficient evidence examples: meeting abstracts without full articles, case reports, or literature that does not adequately represent the patient population, regimen, or clinically meaningful outcomes.

Step Therapy

Step Therapy / Preferred Regimen Guidance for Multiple Myeloma

Evolent does not support Kyprolis-based regimens for newly diagnosed multiple myeloma in transplant-ineligible or certain transplant-eligible settings; alternative regimens recommended by Evolent should be used. For relapsed or refractory multiple myeloma (after 1–3 prior therapies), Kyprolis may be authorized when used in one of the regimens listed below. Providers should follow Evolent step-therapy guidance and preferred regimen recommendations when initiating therapy.

Not supported for newly diagnosed, transplant-ineligible MM: Kyprolis-based regimens (e.g., KRd) due to ENDURANCE trial results and increased cardiotoxicity.
Not supported for newly diagnosed, transplant-eligible MM: Daratumumab + Kyprolis + Revlimid + Dexamethasone (lack of Level 1 evidence over alternative daratumumab + Velcade-based regimens).
For relapsed/refractory MM (after 1–3 prior therapies), Kyprolis may be used in ANY ONE of the following: in combination with dexamethasone; with lenalidomide +/- steroid; with cyclophosphamide +/- steroid; with daratumumab +/- steroid; with pomalidomide +/- steroid.

Denial Risk

Exclusion Criteria and Denial Risks

Exclusion criteria that will trigger denial include disease progression while on Kyprolis, dosing above specified maximum single-dose limits, and investigational or off-label uses lacking sufficient supporting evidence as defined by CMS compendia or acceptable peer-reviewed literature. Examples of insufficient evidence include poor representation of the patient population or regimen in the published evidence, lack of clinically meaningful outcomes, or reliance on uncontrolled case reports or abstracts without full peer-reviewed articles.

Denial triggers: disease progression while taking Kyprolis.
Denial triggers: dosing exceeds single-dose limits (56 mg/m2 twice weekly or 70 mg/m2 once weekly).
Denial triggers: investigational/off-label uses without sufficient evidence per CMS compendia or acceptable peer-reviewed literature.

Background and Evidence

Carfilzomib (Kyprolis) is a proteasome inhibitor indicated for use in multiple myeloma. The policy cites pivotal randomized trials informing coverage decisions, including the ENDURANCE trial (which compared carfilzomib + lenalidomide + dexamethasone to bortezomib + lenalidomide + dexamethasone and found equivalent efficacy but increased cardiotoxicity with carfilzomib) and other large randomized studies that shape the agent’s role in relapsed/refractory disease and newly diagnosed settings. Based on these data and current product labeling, Evolent permits Kyprolis for relapsed or refractory multiple myeloma after 1–3 prior therapies when used in specified combinations (e.g., with dexamethasone; with lenalidomide +/- steroid; with cyclophosphamide +/- steroid; with daratumumab +/- steroid; or with pomalidomide +/- steroid) and restricts certain newly diagnosed uses where evidence does not demonstrate advantage or shows greater toxicity.

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