Currentblue cross blue shield - tennesseePolicy ID_CHS_2025

Carfilzomib (Kyprolis) — Coverage Criteria for Multiple Myeloma and Related Plasma Cell Disorders

Covers medical necessity criteria, dosing limits, and prior authorization requirements for Kyprolis (carfilzomib) for multiple myeloma and related plasma cell disorders for BlueCross BlueShield of Tennessee members.

Policy Summary

Payerblue cross blue shield - tennessee

PolicyCarfilzomib (Kyprolis) — Coverage Criteria for Multiple Myeloma and Related Plasma Cell Disorders

Policy CodePolicy ID_CHS_2025

Change TypeMaterial updates to coverage criteria, dosing limits, and biomarker-directed use

Effective DateJul 31, 202649d

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of t(11;14) when using Kyprolis with venetoclax; approvals may be granted for 12 months when criteria are met.

SourceLink

POLICY UPDATE CHANGES

Authorization criteria expanded to include combination regimens (e.g., isatuximab + lenalidomide + dexamethasone; daratumumab + lenalidomide + dexamethasone) for transplant candidates.

Authorization pathway specifies use with venetoclax and dexamethasone for patients with relapsed/progressive disease and t(11;14) translocation.

Defines dosing ceilings for once-weekly and twice-weekly administration (mg/m2 and absolute mg caps and maximum doses per 28 days).

12 monthsstandard authorization period

70 mg/m2once-weekly ceiling

56 mg/m2twice-weekly ceiling

when applicable

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Coverage Criteria for Carfilzomib (Kyprolis)

Multiple Myeloma - Initial and specific combination/line criteria

Authorization of 12 months may be granted for treatment of multiple myeloma when any of the following criteria are met:

Multiple Myeloma - authorization criteria: Any one of the following: 1) Member is a transplant candidate and will use Kyprolis in primary therapy of symptomatic disease in combination with isatuximab-irfc + lenalidomide + dexamethasone OR daratumumab + lenalidomide + dexamethasone; 2) Member has relapsed or refractory disease with >=3 prior lines and will use Kyprolis in combination with bendamustine + dexamethasone; 3) Member has received >=1 prior line and will use Kyprolis as a single agent; 4) Member has relapsed or progressive disease with documented t(11;14) and will use Kyprolis in combination with venetoclax + dexamethasone; 5) Member has relapsed, refractory, or progressive disease and will use Kyprolis in combination with any of the following: cyclophosphamide + thalidomide + dexamethasone; pomalidomide + dexamethasone; pomalidomide + daratumumab + dexamethasone; daratumumab + dexamethasone; daratumumab + hyaluronidase-fihj + dexamethasone; isatuximab-irfc + dexamethasone; selinexor + dexamethasone; OR dexamethasone alone; 6) Member will use Kyprolis in combination with lenalidomide + dexamethasone OR cyclophosphamide + dexamethasone; 7) Member is a transplant candidate and will use Kyprolis for maintenance therapy in combination with lenalidomide.

Maintains 12-month authorization when criteria met.

Waldenström macroglobulinemia

Authorization of 12 months may be granted for Waldenström macroglobulinemia/lymphoplasmacytic lymphoma when:

Waldenström: Kyprolis used in combination with rituximab and dexamethasone.

12-month authorization.

Systemic light chain amyloidosis

Authorization of 12 months may be granted for systemic light chain amyloidosis when either of the following are met:

Systemic light chain amyloidosis: 1) Kyprolis used in combination with dexamethasone; OR 2) Kyprolis used as a single agent to treat relapsed/refractory non-cardiac disease.

12-month authorization.

POEMS, MIDD, MGRS

Authorization of 12 months may be granted for other plasma cell disorders:

POEMS/MIDD/MGRS: Kyprolis used to treat POEMS syndrome, plasma cell-related MIDD, or plasma cell-related MGRS.

12-month authorization.

Reauthorization

Reauthorization criteria:

Reauthorization: Continued treatment may be reauthorized for 12 months for indications listed in the coverage criteria when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

12-month reauthorization.

Indications for carfilzomib that are not listed as FDA-approved or in accepted compendia are considered experimental/investigational and are not medically necessary. This includes any use outside of the disease states enumerated in compendial resources (see compendial uses).

All indications beyond the FDA‑approved indications and those listed in accepted compendia are considered not medically necessary. Requests for coverage for such indications are subject to denial.

Indication	Regimen / Combination	Coverage status
Multiple myeloma (transplant candidate, primary therapy of symptomatic disease)	Isatuximab-irfc + lenalidomide + dexamethasone	12-month authorization when criteria met
Multiple myeloma (transplant candidate, primary therapy of symptomatic disease)	Daratumumab + lenalidomide + dexamethasone	12-month authorization when criteria met
Multiple myeloma (relapsed/refractory, ≥3 prior lines)	Bendamustine + dexamethasone	12-month authorization when criteria met
Multiple myeloma (single-agent use)	Carfilzomib as single agent for members with ≥1 prior line of therapy	12-month authorization when criteria met
Multiple myeloma (relapsed/progressive with t(11;14))	Venetoclax + dexamethasone	Documentation of t(11;14) required; 12-month authorization when criteria met
Multiple myeloma (relapsed/refractory/progressive)	Cyclophosphamide + thalidomide + dexamethasone	12-month authorization when criteria met
Multiple myeloma (relapsed/refractory/progressive)	Pomalidomide + dexamethasone	12-month authorization when criteria met
Multiple myeloma (relapsed/refractory/progressive)	Pomalidomide + daratumumab + dexamethasone	12-month authorization when criteria met
Multiple myeloma (relapsed/refractory/progressive)	Daratumumab + dexamethasone	12-month authorization when criteria met
Multiple myeloma (relapsed/refractory/progressive)	Daratumumab + hyaluronidase-fihj + dexamethasone	12-month authorization when criteria met
Multiple myeloma (relapsed/refractory/progressive)	Isatuximab-irfc + dexamethasone	12-month authorization when criteria met
Multiple myeloma (relapsed/refractory/progressive)	Selinexor + dexamethasone	12-month authorization when criteria met
Multiple myeloma (relapsed/refractory/progressive)	Dexamethasone alone	12-month authorization when criteria met
Multiple myeloma (combination or other use)	Lenalidomide + dexamethasone	12-month authorization when criteria met
Multiple myeloma (combination or other use)	Cyclophosphamide + dexamethasone	12-month authorization when criteria met
Waldenström macroglobulinemia/lymphoplasmacytic lymphoma	Rituximab + dexamethasone	12-month authorization when criteria met
Systemic light chain amyloidosis	Dexamethasone in combination with carfilzomib	12-month authorization when criteria met
Systemic light chain amyloidosis (relapsed/refractory non-cardiac)	Carfilzomib as single agent	12-month authorization when criteria met
POEMS syndrome, plasma cell-related MIDD, plasma cell-related MGRS	Carfilzomib for treatment of the listed plasma cell disorders	12-month authorization when criteria met

Coding and Dose Limits

Codes referencedmixed

N/A	No procedure or diagnosis codes listed in document

Dose limits (per 28 days and per-dose ceilings)

Once-weekly per-dose ceiling70 mg/m2 per dose (absolute cap 154 mg); maximum 3 doses per 28 days

Twice-weekly per-dose ceiling56 mg/m2 per dose (absolute cap 124 mg); maximum 6 doses per 28 days

ScopeDosing limits apply to all indications and approvals may be subject to these limits in accordance with FDA labeling and compendia

Provider Actions and Authorization Process

Prior Authorization

Prior authorization required

Prior authorization is required. Approvals may be granted for up to 12 months when indication- and regimen-specific criteria are met.

Authorization decisions reference the medical policy manual criteria (effective 2026-07-31).
Reauthorization may be granted for 12 months when there is no evidence of unacceptable toxicity or disease progression on the current regimen.

Step Therapy

Lines of therapy considerations

Coverage depends on prior lines of therapy and the specific regimen requested. No single step-therapy sequence is mandated, but documentation of prior therapies is required to demonstrate eligibility under the applicable criteria.

Relapsed/refractory multiple myeloma: single-agent use allowed after ≥1 prior line of therapy.
Relapsed/refractory multiple myeloma: some combination regimens require ≥3 prior lines of therapy (see medical policy criteria).

Line of Therapy Positioning

first-line | second-line | salvage

Line of therapy notes: Kyprolis coverage by line of therapy: use in relapsed/refractory multiple myeloma as combination therapy for patients who have received 1-3 prior lines (per FDA-approved indications) or as single agent for patients who have received one or more prior lines; policy additionally permits specific combinations after >=3 prior lines and other scenarios as listed.

Biomarker and Genetic Test Requirements

t(11;14) — translocation documentation for venetoclax combinations

Required documentationSubmit documentation of the presence of translocation t(11;14) when using Kyprolis with venetoclax + dexamethasone for relapsed/progressive disease

Use case authorizedKyprolis in combination with venetoclax and dexamethasone is allowed for members with relapsed/progressive disease and documented t(11;14)

Evidence basisAuthorization pathway specifies t(11;14) documentation as a condition for this venetoclax-containing regimen

Key Definitions

Relapsed/Refractory multiple myeloma — definition and policy considerations

DefinitionRelapsed or refractory multiple myeloma: disease that has returned or failed to respond after prior lines of therapy

Policy-specific line requirementsKyprolis covered in combination for patients who have received 1–3 prior lines (per FDA) and as single agent for patients with ≥1 prior line; policy also allows specific combinations after ≥3 prior lines

Authorization periodApprovals for relapsed/refractory multiple myeloma may be granted for 12 months when criteria are met

Compendial contextMultiple myeloma and related plasma cell disorders are listed as compendial uses; other non-listed indications are experimental/investigational and not medically necessary

Background

Carfilzomib (Kyprolis) is a proteasome inhibitor with compendial activity in plasma cell disorders. Compendial uses include multiple myeloma, systemic light chain amyloidosis, Waldenström macroglobulinemia/lymphoplasmacytic lymphoma, POEMS syndrome, and plasma cell‑related MGRS and MIDD. Uses outside these listed indications are treated as experimental/investigational and not medically necessary.

Revision History

2026-07-31policy_effectiveLatest

Medical Policy Manual revision approved and effective; multiple myeloma authorization criteria expanded to list specific combination regimens and maintenance indications with 12-month authorization periods.

2025-09-25last_review

Policy underwent internal review (last_review date recorded).

2025-06reference_update