Commercial

Medical Policy

Notification

Carfilzomib (Kyprolis®)

Notification Issue Date:

This version of the policy will become effective 07/01/2019.
Medical necessity criteria has been revised for multiple myeloma to reflect the United States Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia.

Title:

Carfilzomib (Kyprolis®)

Policy #:

08.01.05m

Policy

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

MEDICALLY NECESSARY

Carfilzomib (Kyprolis) is considered medically necessary and, therefore, covered for the treatment of individuals with any of the following indications:

Multiple myeloma (MM)

Primary therapy for symptomatic MM for transplant candidates in combination with*

Daratumumab, lenalidomide, and dexamethasone
Isatuximab-irfc, lenalidomide, and dexamethasone

Primary therapy for symptomatic MM or for disease relapse after 6 months following primary induction therapy with the same regimen*

In combination with dexamethasone and lenalidomide (National Comprehensive Cancer Network [NCCN]-preferred regimen) when used in the relapse setting; other recommended regimen when used as primary therapy
In combination with dexamethasone and cyclophosphamide as a treatment option for individuals with renal insufficiency and/or peripheral neuropathy

Maintenance therapy for symptomatic MM in combination with lenalidomide for transplant candidates (two-drug maintenance recommended for high-risk disease)*

After response to primary myeloma therapy
For response or stable disease following an autologous hematopoietic cell transplant (HCT)
For response or stable disease following a tandem autologous or allogeneic HCT for high-risk individuals under certain circumstances

Therapy for previously treated myeloma for relapse or progressive disease*

As a single agent for the treatment of individuals with relapsed or refractory MM who have received one or more lines of therapy (FDA)
In combination with dexamethasone and lenalidomide if bortezomib- or anti-CD-38–refractory (NCCN-preferred)
In combination with daratumumab and dexamethasone if bortezomib- or lenalidomide-refractory (NCCN-preferred regimen)
In combination with isatuximab-irfc and dexamethasone if bortezomib- or lenalidomide-refractory (NCCN-preferred regimen)
In combination with dexamethasone and cyclophosphamide
In combination with pomalidomide, and daratumumab and dexamethasone (NCCN-preferred regimen)
In combination with dexamethasone, cyclophosphamide, and thalidomide
In combination with selinexor and dexamethasone
In combination with venetoclax and dexamethasone for individuals with t(11:14)

Therapy for previously treated myeloma for relapsed/refractory disease after three prior lines of therapy in combination with bendamustine and dexamethasone*
For the treatment of individuals with relapsed or refractory MM who have received one to three prior therapies:

In combination with dexamethasone
In combination with lenalidomide and dexamethasone
In combination with daratumumab and dexamethasone
In combination with daratumumab and hyaluronidase-fihj and dexamethasone
In combination with isatuximab and dexamethasone

Systemic Light Chain Amyloidosis

Treatment for all stages in combination with dexamethasone if significant neuropathy for either of the following conditions:

Newly diagnosed disease
Relapsed/refractory disease as a repeat of initial therapy if relapse-free for several years

Treatment for relapsed/refractory noncardiac disease for either of the following regimens:

As a single agent
In combination with dexamethasone

Waldenström macroglobulinemia/lymphoplasmacytic lymphoma

As a component of CaRD (carfilzomib, rituximab [Rituxan], and dexamethasone) regimen for the treatment of individuals with Waldenström macroglobulinemia/lymphoplasmacytic lymphoma as:

Primary therapy
Treatment after relapse if used as primary therapy that was well tolerated and elicited a prolonged response

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome

For the management of symptoms as a substitute for bortezomib in select individuals

*May also be used for the treatment of POEMS, monoclonal immunoglobulin deposition disease (MIDD), and plasma cell–related monoclonal gammopathy of renal significance (MGRS)

EXPERIMENTAL/INVESTIGATIONAL

All other uses for carfilzomib (Kyprolis) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, carfilzomib (Kyprolis) is covered under the medical benefits of the Company's products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Carfilzomib (Kyprolis) was approved by the FDA on July 20, 2012, for the treatment of individuals with multiple myeloma who have received at least two prior therapies including bortezomib (Velcade) and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. Supplemental approvals for carfilzomib (Kyprolis) have since been issued by the FDA.

PEDIATRIC USE

The safety and effectiveness of carfilzomib (Kyprolis) was evaluated in pediatric patients and effectiveness has not been established.

Description

In July 2012, the US Food and Drug Administration (FDA) granted accelerated approval of carfilzomib (Kyprolis [Onyx Pharmaceuticals]), an injectable proteasome inhibitor indicated for the treatment of individuals with multiple myeloma (MM) who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and who have demonstrated disease progression on or within 60 days of completion of the last therapy. Carfilzomib (Kyprolis) is an antineoplastic agent that specifically blocks the activity of the proteasome, which breaks down proteins that are damaged or no longer needed inside healthy cells and cancer cells. This action leads to a buildup of proteins that causes the cancer cells to die, potentially slowing the progression of cancer. Similar to many other cancer therapies, carfilzomib (Kyprolis) is given intravenously.

Subsequently, in July 2015, the FDA approved carfilzomib (Kyprolis) in combination with dexamethasone or with lenalidomide and dexamethasone for the treatment of individuals with relapsed MM who have received one to three prior lines of therapy. The approval was based on a demonstration of improved progression-free survival (PFS) in two multicenter, open-label trials. In study one, 792 individuals with relapsed or refractory MM after one to three lines of prior therapies were randomly assigned to receive lenalidomide and dexamethasone with or without carfilzomib (Kyprolis) for 18 cycles. The individuals in the carfilzomib (Kyprolis), lenalidomide, and dexamethasone arm demonstrated improved PFS (26.3 months) as compared with those in the lenalidomide and dexamethasone arm (17.6 months). Also, the median duration of response was 28.6 months for the 345 individuals achieving a response in the carfilzomib (Kyprolis), lenalidomide, and dexamethasone arm, and 21.2 months for the 264 individuals achieving a response in the lenalidomide and dexamethasone arm. In study two, 929 individuals with relapsed or refractory MM who had received one to three prior therapies were randomly assigned to dexamethasone with carfilzomib (Kyprolis) or bortezomib with dexamethasone. The individuals in the carfilzomib (Kyprolis) with dexamethasone demonstrated an improved PFS (18.7 months) as compared with those in the bortezomib with dexamethasone arm (9.4 months).

In January 2016, the FDA-approved indication for carfilzomib (Kyprolis) was changed to be as a single agent for the treatment of individuals with relapsed or refractory MM who have received one or more prior therapies. This approval was based on three multicenter, single-arm clinical studies. The first study evaluated the efficacy of carfilzomib (Kyprolis) in 24 individuals with relapsed or refractory MM after two or more lines of therapy by duration of response (DOR) and overall response rate (ORR) determined by investigator assessment using the International Myeloma Working Group (IMWG) criteria. The ORR was 50% (four subjects with very good partial response rate, seven subjects with partial response rate, and one subject with stringent complete response rate); the median DOR in individuals who achieved a partial response or better was 8 months. In the second study, 266 individuals with relapsed and refractory MM who had received at least two prior therapies were evaluated based on ORR. Enrolled in the trial were individuals whose disease had a less than or equal to 25% response to the most recent therapy or who had disease progression during or within 60 days of the most recent therapy. ORR was 23% (5% with very good partial response rate, 18% with partial response rate, <1% with complete remission), and median DOR was 7.8 months. The third study evaluated efficacy in 70 individuals with relapsed or refractory MM, who had received one to three prior lines of therapy and had 25% or less response or progression during therapy or within 60 days after the most recent therapy. The ORR, the primary efficacy endpoint, was 50% (26% with very good partial response rate, 23% with partial response rate, and 1% with complete remission).

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

American Hospital Formulary Service–Drug Information (AHFS-DI). c. [LexiComp Web site]. 03/11/2025. Available at: Home - UpToDate® Lexidrug™ [via subscription only]. Accessed September 18, 2025.

Elsevier Gold Standard Clinical Pharmacology Compendium. Carfilzomib. [Clinical Pharmacology Website]. 06/03/2025. Available at: https://www.clinicalkey.com/#!/.[via subscription only]. Accessed September 18, 2025.

Lexi-Drugs Compendium. Carfilzomib (Kyprolis™). 02/04/2025. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed September 18, 2025.

Micromedex® Healthcare Series [Internet database]. Carfilzomib. Greenwood Village, CO: Thomson Micromedex. 07/18/2025. Available at: http://www.micromedexsolutions.com/micromedex2/librarian. Accessed September 18, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Drug and Biologics Compendium. Carfilzomib. [National Comprehensive Cancer Network Web site]. Subscription required. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=385. Accessed September 18, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Multiple Myeloma. Version 2.2026. [NCCN Web site]. 07/16/2025. Available at: http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed September 24, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Systemic Light Chain Amyloidosis. Version 1.2026. [NCCN Web site]. 06/11/2025. Available at: http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed September 18, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma. Version 1.2026. [NCCN Web site]. 06/24/2025. Available at: http://www.nccn.org/professionals/physician_gls/pdf/waldenstroms.pdf. Accessed September 18, 2025.

Onyx Pharmaceuticals. Full Prescribing Information for Kyprolis™ (carfilzomib). Onyx Pharmaceuticals, Thousand Oaks, CA. Onyx Pharmaceuticals Web site. Package labeling. 05/2025 Available at: kyprolis_pi.pdf. Accessed September 18, 2025.

Burke MJ, Ziegler DS, Bautista F, et al. Phase 1b study of carfilzomib with induction chemotherapy in pediatric relapsed/refractory acute lymphoblastic leukemia. Pediatr Blood Cancer. 2022;69(12):e29999. Available at: Phase 1b study of carfilzomib with induction chemotherapy in pediatric relapsed/refractory acute lymphoblastic leukemia - PubMed. Accessed September 18, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. Carfilzomib (Kyprolis™). Approval letter. [FDA Web site]. 07/20/2012 Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed September 18, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. Carfilzomib (Kyprolis™). Labeling. [FDA Web site]. 05/2025. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125276s149lbl.pdf. Accessed September 18, 2025.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

HCPCS Level II Code Number(s)

J9047 Injection, carfilzomib, 1 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 08.01.05m:

11/17/2025

This version of the policy will become effective 11/17/2025.

Medical necessity criteria have been revised for multiple myeloma to reflect the US Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia.

The following criteria have been revised per NCCN:

Multiple myeloma
Systemic light chain amyloidosis

All of the ICD-10 CM codes have been removed from this policy. Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

Revisions From 08.01.05l:

11/18/2024

This version of the policy will become effective 11/18/2024.

Medical necessity criteria have been revised for multiple myeloma to reflect the US Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia.

The following criteria have been revised per NCCN:

Multiple myeloma
Systemic light chain amyloidosis

The following ICD-10 codes have been deleted from this policy as not medically necessary:

C90.10 Plasma cell leukemia not having achieved remission
C90.12 Plasma cell leukemia in relapse

Revisions From 08.01.05k:

10/01/2024

This policy has been identified for the ICD-10 code update, effective 10/01/2024.

The following ICD-10 code has been added to this policy:

C88.00 Waldenstrom macroglobulinemia not having achieved remission

The following ICD-10 code has been deleted from this policy:

C88.0 Waldenstrom macroglobulinemia

Revisions From 08.01.05j:

12/18/2023

This version of the policy will become effective 12/18/2023.

Medical necessity criteria have been revised for multiple myeloma to reflect the National Comprehensive Cancer Network (NCCN) compendia recommendations.

Revisions From 08.01.05i:

11/07/2022

This version of the policy will become effective 11/07/2022

Medical necessity criteria have been revised for multiple myeloma to reflect the United States Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia.

The following criteria have been revised :

Multiple myeloma
Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma
Systemic Light Chain Amyloidosis

Revisions From 08.01.05h:

12/06/2021

This version of the policy will become effective 12/06/2021

Medical necessity criteria have been revised for multiple myeloma to reflect the United States Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia.

The following criteria have been revised :

Multiple myeloma
Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma

The following criteria have been added to the policy:

Systemic Light Chain Amyloidosis

The following ICD-10 code has been added to this policy:

E85.81 Light chain (AL) amyloidosis

Revisions From 08.01.05g:

11/16/2020

This version of the policy will become effective 11/16/2020

Medical necessity criteria have been revised for multiple myeloma to reflect the United States Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia.

Revisions From 08.01.05f:

07/01/2019

Revisions From 08.01.05e:

12/27/2017

This policy has undergone a routine review and the medical necessity criteria have been revised to reflect the United States Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia.

Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date:

11/17/2025

Version Issued Date:

11/17/2025

Version Reissued Date: