Medicare Advantage

Medical Policy

Notification

Carfilzomib (Kyprolis®)

Notification Issued Date:

This version of the policy will become effective 07/21/2019.

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.

Title:

Carfilzomib (Kyprolis®)

Policy #:

MA08.062j

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

Primary therapy for symptomatic multiple myeloma for transplant candidates in combination with daratumumab, lenalidomide, and dexamethasone
Primary therapy for symptomatic myeloma 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 transplant candidates as primary therapy and in the relapse setting; other recommended regimen when used in non-transplant candidates as primary therapy (ixazomib may be substituted for carfilzomib in select individuals)
In combination with dexamethasone and cyclophosphamide (ixazomib may be substituted for carfilzomib in select individuals)

Maintenance therapy for symptomatic multiple myeloma in combination with lenalidomide for transplant candidates

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 multiple myeloma who have received one or more lines of therapy (FDA)
In combination with dexamethasone, given once weekly or twice weekly
In combination with dexamethasone and lenalidomide if bortezomib-refractory
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 patients 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 multiple myeloma 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

For the management of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome as a replacement for bortezomib in select patients

Systemic Light Chain Amyloidosis

Treatment for newly diagnosed disease for all stages in combination with dexamethasone if significant neuropathy
Treatment for relapsed/refractory noncardiac disease

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

ADDITIONAL INDICATIONS

In accordance with the Centers for Medicare & Medicaid Services (CMS) and in addition to the indications above, carfilzomib (Kyprolis), as a part of anticancer chemotherapy regimen, is covered for the following Micromedex Category IIb indications:

Multiple myeloma, Newly diagnosed, transplant-eligible, in combination with an immunomodulatory drug and a steroid
Multiple myeloma, Newly diagnosed, transplant-ineligible, in combination with a chemotherapy agent and a steroid
Waldenström macroglobulinemia

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

There is no Medicare coverage determination addressing this service; therefore, the Company policy is applicable.

BENEFIT APPLICATION

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

Certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when carfilzomib (Kyprolis) is covered under a member's medical benefit (Part B benefit). It does not address instances when carfilzomib (Kyprolis) is covered under a member’s pharmacy benefit (Part D benefit).

US FOOD AND DRUG ADMINISTRATION 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) in pediatric patients have 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 cafilzomib (Kyprolis) for 18 cycles. The individuals in the cafilzomib (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 cafilzomib (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 multiple myeloma 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. Study one 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 multiple myeloma, 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

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Systemic Light Chain Amyloidosis. Version 1.2025. [NCCN Web site].09/13/2024. 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. Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma. Version 1.2025.

[NCCN Web site]. 09/13/2024. Available at: http://www.nccn.org/professionals/physician_gls/pdf/waldenstroms.pdf. Accessed September 24, 2024.

Onyx Pharmaceuticals. Full Prescribing Information for Kyprolis™ (carfilzomib).Onyx Pharmaceuticals, Thousand Oaks, CA. Onyx Pharmaceuticals Web site. Package labeling.

06/2022 Available at: http://pi.amgen.com/united_states/kyprolis/kyprolis_pi.pdf. Accessed September 24, 2024.

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 24, 2024.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA.Carfilzomib (Kyprolis™). Labeling. [FDA Web site]. 06/30/22. Available at:http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process. Accessed September 24, 2024.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

C83.00 Small cell B-cell lymphoma, unspecified site

C83.01 Small cell B-cell lymphoma, lymph nodes of head, face, and neck

C83.02 Small cell B-cell lymphoma, intrathoracic lymph nodes

C83.03 Small cell B-cell lymphoma, intra-abdominal lymph nodes

C83.04 Small cell B-cell lymphoma, lymph nodes of axilla and upper limb

C83.05 Small cell B-cell lymphoma, lymph nodes of inguinal region and lower limb

C83.06 Small cell B-cell lymphoma, intrapelvic lymph nodes

C83.07 Small cell B-cell lymphoma, spleen

C83.08 Small cell B-cell lymphoma, lymph nodes of multiple sites

C83.09 Small cell B-cell lymphoma, extranodal and solid organ sites

C88.0 Waldenstrom macroglobulinemia

C90.00 Multiple myeloma not having achieved remission

C90.02 Multiple myeloma in relapse

C90.20 Extramedullary plasmacytoma not having achieved remission

C90.22 Extramedullary plasmacytoma in relapse

C90.30 Solitary plasmacytoma not having achieved remission

C90.32 Solitary plasmacytoma in relapse

E85.81 Light chain (AL) amyloidosis

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 MA08.062j:

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 MA08.062i:

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 MA08.062h:

12/18/2023

This version of the policy, published on 01/02/2024, will be retroactively effective to 12/18/2023.

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

Revisions From MA08.062g:

01/01/2024	Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.
11/07/2022	This version of the policy will become effective on 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

01/01/2024

Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.

11/07/2022

This version of the policy will become effective on 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 MA08.062f:

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 MA08.062e:

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 MA08.062d:

07/01/2019

This version of the policy will become effective 07/21/2019.
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.

Revisions From MA08.062c:

12/27/2017

Revisions From MA08.062b:

03/23/2016

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling:

Policy criteria for multiple myeloma were updated

Revisions From MA08.062a:

10/21/2015

The following indications were added to this policy as medically necessary based on current US Food and Drug Administration (FDA) labeling and supported off-label uses of carfilzomib (Kyprolis™):

In combination with lenalidomide and dexamethasone in the treatment of individuals with relapsed multiple myeloma who has received one to three prior lines of therapy
In combination with lenalidomide and dexamethasone for a transplant candidate with progressive solitary plasmacytoma or smoldering myeloma (asymptomatic) that has progressed to active (symptomatic) myeloma as:
- Primary chemotherapy
- Therapy on or off clinical trials for disease relapse after 6 months following primary chemotherapy with the same regimen
As therapy for individuals with previously treated multiple myeloma on or off clinical trials for disease relapse or for progressive or refractory disease as:
- A single agent
- In combination with dexamethasone with or without lenalidomide
When used in the treatment of individuals with Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma as a component of CaRD (carfilzomib, rituximab [Rituxan®], and dexamethasone) regimen

The following changes were made to the Coding Table:

Removed all ICD-9 codes
Added ICD-10 codes for Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma

Revisions From MA08.062:

01/01/2015

This is a new policy.

Version Effective Date:

11/18/2024

Version Issued Date:

11/18/2024

Version Reissued Date: