Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Carfilzomib (Kyprolis™)
Policy #:MA08.062d

This policy is applicable to the Company’s Medicare Advantage products only. Policies that are applicable to the Company’s commercial products are accessible via a separate commercial policy database.


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

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.


This Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

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 either of the following indications:
  • Multiple myeloma
    • Primary therapy for active (symptomatic) myeloma or for disease relapse after six months following primary induction therapy with the same regimen
      • In combination with dexamethasone and lenalidomide
      • In combination with dexamethasone and cyclophosphamide for non-transplant candidates
    • Therapy for previously treated myeloma for relapse or progressive disease
      • In combination with dexamethasone , given once weekly or twice weekly (NCCN preferred regimens)
      • In combination with dexamethasone with lenalidomide (NCCN preferred regimens)
      • In combination with dexamethasone and cyclophosphamide
      • In combination with panobinostat for individuals, who have received at least two prior therapies, including bortezomib and an immunomodulatory agent
      • In combination with pomalidomide and dexamethasone for individuals, who have received at least two prior therapies, including an immunomodulatory agent and a proteasome inhibitor and who have demonstrated disease progression on or within 60 days of completion of the last therapy
      • For the treatment of individuals with relapsed or refractory multiple myeloma who has received one to three prior therapies
      • In combination with dexamethasone or with lenalidomide and dexamethasone in the treatment of individuals with relapsed or refractory multiple myeloma
    • As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
  • Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma
    • When used in the treatment of individuals with Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma as a component of CaRD (carfilzomib, rituximab [Rituxan®], and dexamethasone) regimen as:
      • Primary therapy
      • For treatment of relapse after at least 24 months of response if used as primary therapy

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.
Policy 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 brentuximab vedotin (Adcetris®) is covered under a member's medical benefit (Part B benefit). It does not address instances when brentuximab vedotin (Adcetris®) 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 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.

In January 2016, FDA-approved indication for carfilzomib (Kyprolis™) was changed to be as a single agent for the treatment of individuals with relapsed or refractory multiple myeloma 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 multiple myeloma after 2 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% (4 subjects with very good partial response rate, 7 subjects with partial response rate, and 1 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 multiple myeloma who had received at least two prior therapies efficacy 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, less than 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 overall response rate, the primary efficacy endpoint, was 50% (26% with very good partial response rate, 23% with partial response rate, and 1% with complete remission).

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 multiple myeloma 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 multiple myeloma after one to three lines of prior therapies were randomized 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 randomized 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).

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). Carfilzomib. [LexiComp Web site]. 02/22/2019. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed MAY 8, 2019.

Carfilzomib. Micromedex® Healthcare Series. Greenwood Village, CO: Thomson Micromedex. Available at: http://www.micromedexsolutions.com/micromedex2/librarian/ http://www.thomsonhc.com/[via subscription only]. 03/04/2019. Accessed MAY 8, 2019.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Carfilzomib. [Clinical Pharmacology Website]. 04/22/2019. Available at: https://www.clinicalkey.com/#!/.[via subscription only]. Accessed MAY 8, 2019.

Lexi-Drugs Compendium. Carfilzomib (Kyprolis™). 05/02/2019. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed MAY 8, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma. Version 2.2019. Available at: http://www.nccn.org/professionals/physician_gls/pdf/waldenstroms.pdf. Accessed MAY 8, 2019.

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 MAY 8, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Multiple Myeloma. Version 2.2019. Available at: http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed MAY 8, 2019.

Onyx Pharmaceuticals. Full Prescribing Information for Kyprolis™ (carfilzomib). Onyx Pharmaceuticals, Thousand Oaks, CA. Onyx Pharmaceuticals Web site. Package labeling. 02/2019 Available at: http://pi.amgen.com/united_states/kyprolis/kyprolis_pi.pdf. Accessed MAY 8, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. Carfilzomib (Kyprolis™). Approval letter. [FDA Web site]. 07/20/20112 Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm Accessed MAY 8, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. 02/28/19 Carfilzomib (Kyprolis™). Labeling. [FDA Web site]. 02/28/19. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process. Accessed MAY 8, 2019.



Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


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



HCPCS Level II Code Number(s)

J9047 Injection, carfilzomib, 1 mg




Revenue Code Number(s)

N/A

Coding and Billing Requirements






Policy History

MA08.062d
07/01/2019This 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.

MA08.062c
12/27/2017This 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.

MA08.062b
03/23/2016This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling:
  • Policy criteria for multiple myeloma was updated

MA08.062a
10/21/2015The 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

MA08.062
01/01/2015This is a new policy.




Version Effective Date: 07/01/2019
Version Issued Date: 07/01/2019
Version Reissued Date: N/A