Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Talimogene laherparepvec (Imlygic™)

Policy #:08.01.27d

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

Talimogene laherparepvec (Imlygic™) is considered medically necessary and, therefore, covered for individuals with melanoma who are not pregnant or immunocompromised when any of the following criteria are met:
  • Intralesional treatment for unresectable cutaneous, subcutaneous, and nodal lesions in individuals with histologically confirmed stage IIIB, IIIC, or IV recurrent melanoma after initial surgery
  • First-line and/or second-line intralesional treatment for unresectable stage III melanoma with clinical satellites or in-transit metastases
  • Intralesional treatment for unresectable distant metastatic disease (extracranial lesions)
  • First-line and/or second-line intralesional treatment of unresectable local, satellite and/or in-transit recurrence
  • Intralesional treatment for unresectable or incomplete resection of nodal recurrence

According to the FDA-approved label, conditions indicative of an individual being immunocompromised include those with a history of primary or acquired immunodeficient states, leukemia, lymphoma, AIDS or other clinical manifestations of infection with human immunodeficiency viruses, and those on immunosuppressive therapy.

EXPERIMENTAL/INVESTIGATIONAL

All other uses for talimogene laherparepvec (Imlygic) 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.

COURSE OF TREATMENT AND DOSAGE AND FREQUENCY FOR TALIMOGENE LAHERPAREPVEC (IMLYGIC)

Per the US Food and Drug Administration (FDA) labeling, treatment with talimogene laherparepvec (Imlygic) is as follows:
  • Treatment course of at least six months unless other treatment is required or until there are no injectable lesions to treat
  • After six months of treatment, individuals may continue treatment until clinically relevant disease progression (i.e., disease progression associated with a decline in performance status and/or alternative therapy is required), up to 12 months
  • Individuals experiencing a response at 12 months after the start of treatment could continue treatment for up to an additional 6 months, unless there are no remaining injectable lesions or disease progression

Per the FDA labeling, the total injection volume for each talimogene laherparepvec (Imlygic) treatment is not to exceed 4 mL for all injected lesions combined, both at the time of initial treatment and subsequent treatments. It may not be possible to inject all lesions at each treatment visit or over the full course of treatment. Previously injected and/or uninjected lesion(s) may be injected at subsequent treatment visits.
  • The recommended dose for initial treatment with talimogene laherparepvec (Imlygic) is up to 4 mL at a concentration of 106 (1 million) plaque-forming units (PFU) per mL.
  • The recommended dose for subsequent administrations of talimogene laherparepvec (Imlygic) is up to 4 mL at a concentration of 108 (100 million PFU) per mL. The second treatment is to be performed three weeks after the initial treatment and all subsequent treatments are to be performed two weeks after the previous treatment.

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 service.
Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, talimogene laherparepvec (Imlygic) 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

Talimogene laherparepvec (Imlygic) was approved by the FDA on October 27, 2015 for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in individuals with melanoma recurrent after initial surgery.

PEDIATRIC USE

The safety and effectiveness of talimogene laherparepvec (Imlygic) in pediatric patients have not been established.

Description

Talimogene laherparepvec (Imlygic) is a first-in-class oncolytic viral therapy that received US Food and Drug Administration (FDA) approval on October 27, 2015 for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in individuals with melanoma recurrent after initial surgery. Talimogene laherparepvec (Imlygic) is a live, attenuated herpes simplex virus type 1 (HSV-1) that has been genetically modified to replicate within tumors and express granulocyte macrophage colony-stimulating factor (GM-CSF), an immunostimulatory protein. The administration of talimogene laherparepvec (Imlygic) causes cell lysis of tumors, followed by the release of tumor-derived antigens. The antigens along with the virally derived GM-CSF may promote an anti-tumor immune response.

The safety and efficacy of talimogene laherparepvec (Imlygic) was evaluated in a multicenter study of 436 participants with metastatic stage IIIB, IIIC, and IV melanoma that could not be surgically resected. The OPTiM study compared talimogene laherparepvec (Imlygic), administered by intralesional injection, with the subcutaneously administered granulocyte macrophage colony-stimulating factor (GM-CSF). The major efficacy outcome was durable response rate (DRR), defined as the percent of patients with complete response or partial response maintained continuously for a minimum of six months. Overall response rate (ORR) and overall survival (OS) were also identified. The DRR was 16.3% in individuals treated with talimogene laherparepvec (Imlygic) compared with 2.1% who received GM-CSF. The ORR was also higher in the talimogene laherparepvec (Imlygic) arm (26.4%) as compared to GM-CSF (5.7%). There was no statistically significant difference in OS between the two arms. The median OS in the talimogene laherparepvec (Imlygic) group was 23.3 months and 18.9 months in the GM-CSF group. The most common adverse events associated with talimogene laherparepvec (Imlygic) were fatigue, chills, pyrexia, injection site pain, and nausea.

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


Adam J, Robertson J, Donegan E, et al. NICE guidance for talimogene iaherparepvec for unresectable metastatic melanoma. Lancet Oncol. 2016;17(11):1485-1486.

American Cancer Society (ACS). Melanoma skin cancer stages. [ACS Web site]. 12/14/2017. Available at: http://www.cancer.org/cancer/skincancer-melanoma/detailedguide/melanoma-skin-cancer-stages. Accessed February 12, 2018.

Amgen®. Full Prescribing Information for Imlygic. Thousand Oaks, CA. Amgen Website. August 2017. Available at: https://pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/imlygic/imlygic_pi.pdf. Accessed February 12, 2018.

Andtbacka RH, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33:2780-2788.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Talimogene laherparepvec. [ClinicalKey Web site]. August 1, 2017. Available at: https://www.clinicalkey.com/. [via subscription only]. Accessed February 12, 2018.

Lexi-Drugs Compendium. Talimogene laherparepvec. [Lexicomp Online Web site]. February 5, 2018. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed February 13, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Melanoma. V2.2018. January 19, 2018. Available at: http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf. Accessed February 12, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Drug and Biologics Compendium. Talimogene laherparepvec. [National Comprehensive Cancer Network Web site]. Subscription required. Available at: https://www.nccn.org/professionals/drug_compendium/content/. Accessed February 7, 2018.

Talimogene laherparepvec (Imlygic™). American Hospital Formulary Service (AHFS). AHFS Drug Information 2017. 03/08/2017. [Lexicomp Web site]. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/complete_ashp/6057691. [via subscription only]. Accessed February 13, 2018.

Truven Health Analytics Inc. Micromedex® 2.0 Healthcare Series. Talimogene laherparepvec. [Micromedex Web site]. 08/03/2017. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed February 13, 2018.

US Food and Drug Administration (FDA). Center for Biologics Evaluation and Research. Imlygic. [FDA Web site]. Available at: http://www.fda.gov/biologicsbloodvaccines/cellulargenetherapyproducts/approvedproducts/ucm469411.htm. Accessed February 13, 2018.

US Food and Drug Administration (FDA). Center for Biologics Evaluation and Research. Imlygic. Package insert. [FDA Web site]. 10/2015. Available at: http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM469575.pdf. Accessed February 13, 2018.

US Food and Drug Administration (FDA). Center for Biologics Evaluation and Research. Imlygic. Approval letter. [FDA Web site]. 10/27/2015. Available at:
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM469670.pdf. Accessed February 13, 2018.





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)

C43.0 Malignant melanoma of lip

C43.10 Malignant melanoma of unspecified eyelid, including canthus

C43.111 Malignant melanoma of right upper eyelid, including canthus

C43.112 Malignant melanoma of right lower eyelid, including canthus

C43.121 Malignant melanoma of left upper eyelid, including canthus

C43.122 Malignant melanoma of left lower eyelid, including canthus

C43.20 Malignant melanoma of unspecified ear and external auricular canal

C43.21 Malignant melanoma of right ear and external auricular canal

C43.22 Malignant melanoma of left ear and external auricular canal

C43.30 Malignant melanoma of unspecified part of face

C43.31 Malignant melanoma of nose

C43.39 Malignant melanoma of other parts of face

C43.4 Malignant melanoma of scalp and neck

C43.51 Malignant melanoma of anal skin

C43.52 Malignant melanoma of skin of breast

C43.59 Malignant melanoma of other part of trunk

C43.60 Malignant melanoma of unspecified upper limb, including shoulder

C43.61 Malignant melanoma of right upper limb, including shoulder

C43.62 Malignant melanoma of left upper limb, including shoulder

C43.70 Malignant melanoma of unspecified lower limb, including hip

C43.71 Malignant melanoma of right lower limb, including hip

C43.72 Malignant melanoma of left lower limb, including hip

C43.8 Malignant melanoma of overlapping sites of skin

C43.9 Malignant melanoma of skin, unspecified



HCPCS Level II Code Number(s)

J9325 Injection, talimogene laherparepvec, per 1 million plaque forming units


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

Revisions from 08.01.27d
10/01/2018This policy has been identified for the ICD-10 CM code update, effective 10/01/2018.

The following CD-10 CM codes have been termed from this policy:
C43.11 Malignant melanoma of right eyelid, including canthus

C43.12 Malignant melanoma of left eyelid, including canthus


The following ICD-10 CM codes have been added to this policy:
C43.111 Malignant melanoma of right upper eyelid, including canthus

C43.112 Malignant melanoma of right lower eyelid, including canthus

C43.121 Malignant melanoma of left upper eyelid, including canthus

C43.122 Malignant melanoma of left lower eyelid, including canthus



Revisions from 08.01.27c
04/09/2018This 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: 10/01/2018
Version Issued Date: 10/01/2018
Version Reissued Date: N/A

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