Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Carfilzomib (Kyprolis™)

Policy #:08.01.05e

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


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. 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.

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 Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

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

MEDICALLY NECESSARY

Carfilzomib (Kyprolis™) is considered medically necessary and, therefore, covered for either of the following indications:
  • Multiple myeloma
    • As a single agent in the treatment of an individual with relapsed or refractory multiple myeloma who has received one or more prior therapies
    • In combination with dexamethasone or with lenalidomide and dexamethasone in the treatment of an individual with relapsed or refractory multiple myeloma who has received one to three prior lines of therapy
    • In combination with dexamethasone and lenalidomide or dexamethasone and cyclophosphamide for non-transplant individuals, as primary therapy for active (symptomatic) myeloma or for disease relapse after 6 months following primary induction therapy with the same regimen
    • As therapy for an individual with previously treated multiple myeloma for disease relapse or for progressive disease:
      • In combination with dexamethasone with or without lenalidomide
      • In combination with dexamethasone and cyclophosphamide
      • In combination with panobinostat for individuals who have received at least two prior regimens 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 have demonstrated disease progression on or within 60 days of completion of last therapy
  • Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma
    • When used in the treatment of an individual 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.
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 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]. 03/08/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed November 15, 2017.

Carfilzomib. Micromedex® Healthcare Series. Greenwood Village, CO: Thomson Micromedex. Available at: http://www.micromedexsolutions.com/micromedex2/librarian/ http://www.thomsonhc.com/[via subscription only]. 10/17/2017. Accessed November 15, 2017.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Carfilzomib. [Clinical Pharmacology Website]. 10/03/2017. Available at: https://www.clinicalkey.com/#!/.[via subscription only]. Accessed November 15, 2017.

Lexi-Drugs Compendium. Carfilzomib (Kyprolis). 11/08/2017. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed November 15, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma. Version 1.2017. Available at: http://www.nccn.org/professionals/physician_gls/pdf/waldenstroms.pdf. Accessed November 13, 2017.

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 November 13, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Multiple Myeloma. Version 2.2018. Available at: http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed November 13, 2017.

Onyx Pharmaceuticals. Full Prescribing Information for Kyprolis™ (carfilzomib). Onyx Pharmaceuticals, Thousand Oaks, CA. Onyx Pharmaceuticals Web site. Available at: http://pi.amgen.com/united_states/kyprolis/kyprolis_pi.pdf. Accessed November 13, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. Kyprolis™ . [FDA Web site]. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed November 14, 2017.





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


Cross References


Policy History

08.01.05e:
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.

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

Version Effective Date: 12/27/2017
Version Issued Date: 12/27/2017
Version Reissued Date: N/A

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