ModifiedCentenePolicy CP.PHAR.309

Clinical Policy: Carfilzomib (Kyprolis)

Defines Centene medical necessity and prior authorization criteria for Kyprolis (carfilzomib) for adults with multiple myeloma and specified off-label hematologic indications; applies to Commercial, HIM, and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyCarfilzomib (Kyprolis) clinical coverage criteria

Policy CodePolicy CP.PHAR.309

Change TypeMaterial updates (regimen additions and clarifications)

Effective DateFeb 1, 2017

Next Review DateNov 25, 2024

Key ActionProvider must obtain prior authorization and submit clinical documentation supporting that the member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

Added option for Kyprolis to be prescribed in combination with Sarclisa for multiple myeloma primary treatment.

Revised relapse/refractory multiple myeloma prescribing regimens to add hematologist as prescriber option and clarify 'one to three lines of therapy'.

Added regimen option combining carfilzomib with venetoclax and dexamethasone for patients with t(11;14) translocation.

J9047HCPCS code

1–3FDA indication lines

56 mg/m2Max twice-weekly dose

70 mg/m2Max once-weekly dose

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Coverage Criteria

inv-05: MM initial and relapse/refractory therapy — Covered when regimen‑specific dosing and indication criteria are met for multiple myeloma or related diagnoses per NCCN and policy updates.

Covered when regimen‑specific dosing and indication criteria are met for multiple myeloma or related diagnoses per NCCN and policy updates.

General dosing requirement: Kyprolis must be dosed per specified regimen schedules: e.g., once-weekly 20/70 mg/m2 (start 20 mg/m2 then escalate to 70 mg/m2 if tolerated) or twice-weekly 20/56 mg/m2 (start 20 mg/m2 then escalate to 56 mg/m2 if tolerated), or regimen-specific 20/27 mg/m2 schedules where applicable; calculate dose using body surface area and follow infusion timing per prescribing information; dose limits apply by regimen.see dosing schedules

See Section V for regimen specifics

Combination regimens: Coverage includes Kyprolis as monotherapy or in combination with dexamethasone, lenalidomide, daratumumab (including Darzalex Faspro), isatuximab (Sarclisa), selinexor, cyclophosphamide (± thalidomide), pomalidomide (± daratumumab), venetoclax for t(11;14), bendamustine for late relapse, and other NCCN-listed agents per Appendix B and updates.regimen listed in Appendix B or updated NCCN-based additions

New combinations added over reviews include sarclisa and venetoclax (for t(11;14)).

Relapsed/Refractory MM criteria: For relapsed/refractory MM regimens, use aligns with one to three lines of therapy for specified combinations (documentation of prior lines may be required), hematologist may be listed as prescriber, and progression should be supported by IMWG criteria when applicable.one to three prior lines as applicable

Policy updated 4Q 2024 to clarify lines of therapy and prescriber role

Non‑FDA approved indications that are not specifically addressed within this clinical policy are not authorized for coverage unless the provider supplies sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies. Providers should reference the plan’s off‑label use policies (e.g., CP.CPA.09, HIM.PA.154, CP.PMN.53) and submit supporting evidence when requesting coverage for an off‑label indication.

Non‑FDA approved indications that do not appear in this policy are excluded from coverage unless the request is supported by the plan’s off‑label use policy or other evidence documents demonstrating efficacy and safety. Requests for such indications must include relevant guideline or peer‑reviewed literature and meet the documentation requirements described in the off‑label policies.

For members covered under Medicaid, any applicable state Medicaid coverage provisions supersede the coverage provisions in this clinical policy when there is a conflict. Providers should consult the state Medicaid manual for specific coverage rules that may apply.

Use of carfilzomib for indications outside those listed in this policy may be considered not medically necessary if the provider does not supply sufficient documentation of efficacy and safety per the plan’s off‑label use policies. Absent that documentation, such requests are subject to denial.

Covered Regimens

Regimen	Indication / Notes	Coverage status
Kyprolis + lenalidomide + dexamethasone
Kyprolis + dexamethasone
Kyprolis + daratumumab + dexamethasone (includes daratumumab/hyaluronidase-fihj, Darzalex Faspro)
Kyprolis + isatuximab (Sarclisa) + dexamethasone
Kyprolis as single agent

Regimen / Combination	Required biomarker or patient selection (if any)	Coverage status / Notes
Kyprolis + dexamethasone (± lenalidomide)
Kyprolis + daratumumab (± hyaluronidase) + dexamethasone
Kyprolis + isatuximab (Sarclisa) + dexamethasone
Kyprolis + selinexor + dexamethasone
Kyprolis + cyclophosphamide (with or without thalidomide) + dexamethasone
Kyprolis + pomalidomide ± daratumumab + dexamethasone
Kyprolis + venetoclax + dexamethasone
Kyprolis + bendamustine + dexamethasone (for late relapse after ≥3 prior therapies)

Example regimen	Context / notes	Coverage status
Carfilzomib + dexamethasone
Carfilzomib + lenalidomide + dexamethasone
Carfilzomib + cyclophosphamide + dexamethasone
Daratumumab + carfilzomib + lenalidomide + dexamethasone
Carfilzomib in combination with Sarclisa (isatuximab) or daratumumab Faspro
Venetoclax + dexamethasone for patients with t(11;14)
Various other NCCN-listed combinations (see Appendix B)

Coding and Dosing Highlights

HCPCS CodesHCPCSCovered

J9047

Injection, carfilzomib, 1 mg

Kyprolis dosing escalation thresholds (inv-11)

Starting dose20 mg/m2 (initiate on Cycle 1 Day 1 or Days 1 and 2 depending on schedule)

Escalation — twice‑weekly regimenEscalate to 56 mg/m2 (if tolerated) on Day 8 of Cycle 1 for the 20/56 mg/m2 twice‑weekly schedule

Escalation — once‑weekly regimenEscalate to 70 mg/m2 (if tolerated) on Day 8 of Cycle 1 for the 20/70 mg/m2 once‑weekly schedule

Cycle length and infusion28‑day cycles; IV infusion (commonly 30‑minute or 10‑minute per regimen specifics)

Provider Actions and Administrative Requirements

Prior Authorization

Prior Authorization Requirement

Prior authorization may be required for specified Kyprolis (carfilzomib) regimens. Providers must obtain prior authorization and supply supporting evidence when the requested regimen, dose, or line of therapy is subject to PA per this clinical policy and the member’s line of business.

Prior authorization required for certain regimens (see policy criteria for primary, maintenance, and previously treated MM).
Providers should follow the plan’s prior authorization process and submit all required clinical documentation.

Documentation Required

Supporting Clinical Documentation

Providers must submit documentation (e.g., office chart notes, laboratory results, imaging, pathology reports, treatment history) demonstrating that the member meets all approval criteria. Failure to provide adequate supporting clinical documentation may result in denial or delay.

Definitions

Carfilzomib (Kyprolis) — definition (inv-26)

Drug classCarfilzomib (Kyprolis) — a proteasome inhibitor

Primary FDA indicationTreatment of adult patients with relapsed or refractory multiple myeloma (MM) as specified (combination regimens after 1–3 prior lines or single‑agent after ≥1 prior therapy)

Usage contextsApproved for specified combination regimens (e.g., with lenalidomide/dexamethasone, dexamethasone alone, daratumumab combinations, isatuximab combinations) and as single‑agent therapy per labeling and NCCN guidance

CaRD — regimen definition (inv-27)

AcronymCaRD — carfilzomib, rituximab, dexamethasone

Clinical contextRegimen described as a combination option used in Waldenstrom's macroglobulinemia / lymphoplasmacytic lymphoma contexts

Line of Therapy

inv-28: second-line — 1 top-level node

Second-line (combination): Combination use in relapsed/refractory multiple myeloma for patients who have received one to three lines of therapy as specified in the FDA indications and policy (e.g., Kyprolis with lenalidomide + dexamethasone; with dexamethasone; with daratumumab + dexamethasone; with isatuximab + dexamethasone).

inv-29: salvage — 1 top-level node

Salvage (single-agent): Single-agent Kyprolis for relapsed/refractory multiple myeloma in adults who have received one or more prior lines of therapy (per FDA indication).

inv-30: first-line | second-line — 2 top-level nodes

First-line (primary therapy):

Biomarker Requirements

t(11;14) — biomarker reference (inv-31)

Markert(11;14)

Role in policyBiomarker referenced for selection of venetoclax combination with carfilzomib (coverage contingent on t(11;14) presence)

Associated regimenCarfilzomib combined with venetoclax and dexamethasone in patients with t(11;14)

t(11;14) — biomarker reference (inv-32)

Biomarkert(11;14)

Policy implicationRequired for consideration of the carfilzomib + venetoclax + dexamethasone regimen; documentation of translocation should be provided

Reference to updates

Background

Carfilzomib (Kyprolis) is a proteasome inhibitor indicated for the treatment of adult patients with relapsed or refractory multiple myeloma. It may be used as combination therapy (for patients who have received one to three prior lines of therapy depending on the regimen) or as a single agent for patients with ≥1 prior therapy. The policy also recognizes selected off‑label hematologic indications (for example, Waldenstrom’s macroglobulinemia and systemic light‑chain amyloidosis) when supported by practice guidelines or peer‑reviewed evidence and appropriate documentation.