Medicare Advantage

Medical Policy

Title:

Lifileucel (Amtagvi™)

Policy #:

MA08.172

Policy

In the absence of coverage criteria from applicable Medicare statutes, regulations, NCDs, LCDs, CMS manuals, or other Medicare coverage documents, this policy uses internal coverage criteria developed by the Company in consideration of peer-reviewed medical literature, clinical practice guidelines, and/or regulatory status.

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.

MEDICALLY NECESSARY

Lifileucel (Amtagvi) as a component of tumor-infiltrating lymphocyte (TIL) therapy is considered medically necessary and, therefore, covered in adult individuals with unresectable or metastatic melanoma* and all of the following:

as second-line or subsequent systemic therapy** as National Comprehensive Cancer Network (NCCN)-preferred therapy after progression on both

PD-1 blocking antibody (e.g., Keytruda, Opdivo) and
BRAF inhibitor (e.g., (e.g., Braftovi, Tafinlar, Zelboraf) with or without a MEK inhibitor (e.g., Cotellic, Mekinist, Mektovi) if BRAF V600 mutation positive.

Eastern Cooperative Oncology Group (ECOG) performance status score of PS 0 or 1
The individual has at least one resectable lesion (or aggregate of lesions resected) of a minimum 1.5 cm in diameter, post-resection, to generate cell therapy
The individual has adequate and stable kidney, pulmonary and cardiac function
The individual does not have clinically significant active systemic infection
The individual does not have uncontrolled brain metastasis
The individual does not have uveal or ocular melanoma
The individual does not have a history of prior cell transfer therapy

Note: one-time lifileucel TIL cell therapy

*metastatic disease includes stage III unresectable/borderline resectable disease with clinically positive node(s) or clinical satellite/in-transit metastases, or as well as unresectable/borderline resectable local satellite/in-transit recurrence, unresectable nodal recurrence, and widely disseminated distant metastatic disease
**systemic therapy is preferred for unresectable or widely disseminated distant metastatic disease

EXPERIMENTAL/INVESTIGATIONAL

All other uses for lifileucel (Amtagvi) not identified in this policy 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.

NOT ELIGIBLE FOR SEPARATE REIMBURSMENT

The harvesting and preparation of blood-derived T lymphocytes and the receipt and preparation of T cells are not eligible for separate reimbursement from the TIL administration.

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

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

BENEFIT APPLICATION

Subject to the applicable Evidence of Coverage, lifileucel (Amtagvi) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in the medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Lifileucel (Amtagvi) was approved by the FDA on February 16, 2024, for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a programmed cell death protein-1 (PD-1)–blocking antibody, and if BRAF V600 mutation–positive, a BRAF inhibitor with or without an MEK inhibitor.

DOSING GUIDELINES

LIFILEUCEL (AMTAGVI)
Pre-treatment

Lymphodepleting chemotherapy: cyclophosphamide 60 mg/kg intravenous (IV) daily with mesna for 2 days followed by fludarabine 25 mg/m² intravenous (IV) daily for 5 days.

Treatment*: For autologous use only. For IV only.
Lifileucel (Amtagvi) target dose is 7.5 × 10⁹ to 72 × 10⁹ viable cells.

*Amtagvi infusion should follow as soon as possible after 24 hours have passed since the last dose of fludarabine but must not exceed 4 days.

Post-treatment

IL-2 (aldesleukin) or Proleukin at 600,000 IU/kg every 8 to 12 hours for up to 6 doses (3 to 24 hours after infusion) to support cell expansion in vivo.

Administer in an inpatient hospital setting with an intensive care facility.

PEDIATRIC USE

The safety and effectiveness of lifileucel (Amtagvi) have not been established in pediatric individuals less than 18 years of age.

Description

Malignant melanoma is a common skin cancer that occurs due to the uncontrolled growth of the melanin cells (melanocytes) within the upper layer of the skin (epidermis) or from similar cells that may be found in moles (nevi). Melanoma is less common (accounts for only about 1%) than other skin cancers such as basal cell carcinoma and squamous cell carcinoma, but causes a large majority of skin cancer deaths. Melanomas have high metastatic potential and utilize the host microenvironment to promote tumor growth and spread to other organs. About one-half of all melanomas have mutations in the BRAF gene; melanoma cells with these mutations make an altered BRAF protein that helps them grow. The MEK (mitogen-activated protein kinase kinase) and BRAF proteins work together, so drugs that inhibit MEK can be used to treat melanomas with BRAF mutation. Currently, there are no approved treatments for patients with metastatic melanoma whose condition worsens while on or after treatment with immune checkpoint inhibitors and BRAF/MEK inhibitors, assuming they have a BRAF V600 mutation.

Lifileucel (Amtagvi) is a tumor-derived autologous T-cell immunotherapy and the first cellular therapy approved for unresectable or metastatic melanoma. It is manufactured using tumor-infiltrating leukocyte (TIL) cells that are collected from a patient's tumor tissue, treated in culture, and then infused back to the patient following lymphodepletion. The specific mechanism of action is unknown. After lifileucel (Amtagvi) infusion, the patient receives a short course of aldesleukin (Proleukin).

PEER-REVIEW LITERATURE

SUMMARY

The safety and efficacy of a single treatment of lifileucel (Amtagvi) was evaluated in a Phase 2 global, multicenter, multicohort, open-label, single-arm (C-144-01) trial. The trial included participants with unresectable or metastatic melanoma who had previously received one or more systemic therapies, including anti-PD-1/PD-L1 and a BRAF inhibitor with or without a MEK inhibitor for those with a BRAF V600 mutation. All 73 (100%) patients who underwent tumor resection and received the recommended dose of lifileucel (Amtagvi) received prior anti-PD-(L)1 therapy, 63 (86.3%) received prior anti-CTLA-4 therapy, 42 (57.5%) received anti-PD1/anti-CTLA-4 combination therapy and 20 (27.4%) received a BRAF inhibitor or combination therapy with BRAF and MEK inhibitors. Among the primary efficacy analysis set of 73 patients in Cohort 4 who received lifileucel (Amtagvi) at the recommended dose (7.5 × 109 to 72 × 109 viable cells), the objective response rate (ORR) was 31.5% and the median duration of response (DOR) was not reached at 18.6 months follow-up. Of this, 4.1% of participants had a complete response and 27.4% have had a partial response. The median prior lines of therapy were three, and 43.5% of participants had a DOR of at least 12 months. Among a pooled efficacy set of 153 patients from Cohorts 2 and 4 who received the recommended Amtagvi dose, the ORR was 31.4% and the median DOR was not reached at 21.5 months follow-up.

OFF-LABEL INDICATIONS

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

References

Cancer stat facts: melanoma of the skin. National Cancer Institute. https://seer.cancer.gov/statfacts/html/melan.html. Accessed August 19, 2024.

American Hospital Formulary Service (AHFS). Drug Information. 2024. Lifileucel. [LexiDrugs website]. 08/02/2024. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 19, 2024.

Chesney J, Lewis KD, Kluger H, et al. Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. J Immunother Cancer. 2022;10(12):e005755.

Elsevier's Clinical Pharmacology Compendium. Lifileucel (Amtagvi). [Clinical Key Web site]. 08/24/23. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed August 19, 2024.

Lexi-Drugs Compendium. Lifileucel. [Lexicomp Online Web site]. 06/05/2024. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 19, 2024.

Micromedex® Healthcare Series [Internet database]. Lifileucel. Greenwood Village, CO: Thomson Micromedex. 03/07/2024. Available at: http://www.micromedexsolutions.com/micromedex2/librarian. Accessed August 19, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology – Melanoma: Cutaneous. V2.2024. [NCCN Web site]. 04/03/2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf [via subscription only]. Accessed August 16, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Drugs and Biologics Compendium. Lifileucel. [NCCN Web site]. 2024. Available at: https://www.nccn.org/professionals/drug_compendium/content [via subscription only]. Accessed August 16, 2024.

Product Information: AMTAGVI suspension for intravenous infusion, lifileucel suspension for intravenous infusion. 02/2024. Iovance Biotherapeutics Manufacturing LLC (per FDA), Philadelphia, PA, 2024. Accessed August 20, 2024.

Sarnaik AA, Hamid O, Khushalani NI, et al. Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma. J Clin Oncol. 2021;39(24):2656-2666.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

C43.0 Malignant melanoma of lip

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

C43.21 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

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

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

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

C44.89 Other specified malignant neoplasm of overlapping sites of skin

C44.99 Other specified malignant neoplasm of skin, unspecified

C51.0 Malignant neoplasm of labium majus

C51.1 Malignant neoplasm of labium minus

C51.2 Malignant neoplasm of clitoris

C51.8 Malignant neoplasm of overlapping sites of vulva

C51.9 Malignant neoplasm of vulva, unspecified

C52 Malignant neoplasm of vagina

C57.7 Malignant neoplasm of other specified female genital organs

C57.8 Malignant neoplasm of overlapping sites of female genital organs

C57.9 Malignant neoplasm of female genital organ, unspecified

C60.0 Malignant neoplasm of prepuce

C60.1 Malignant neoplasm of glans penis

C60.2 Malignant neoplasm of body of penis

C60.8 Malignant neoplasm of overlapping sites of penis

C60.9 Malignant neoplasm of penis, unspecified

C63.2 Malignant neoplasm of scrotum

C63.7 Malignant neoplasm of other specified male genital organs

C63.8 Malignant neoplasm of overlapping sites of male genital organs

C63.9 Malignant neoplasm of male genital organ, unspecified

HCPCS Level II Code Number(s)

THE FOLLOWING CODES ARE USED TO REPRESENT LIFILEUCEL (AMTAGVI™):

C9399 Unclassified drugs or biologicals

J3590 Unclassified biologics

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From MA08.172:

10/28/2026	The policy has been reviewed and reissued to communicate the Company's continuing position on lifileucel (Amtagvi™).
09/03/2025	The policy has been reviewed and reissued to communicate the Company's continuing position on lifileucel (Amtagvi™).
10/21/2024	The following new policy has been developed to communicate the Company's coverage criteria for lifileucel (Amtagvi).

Version Effective Date:

10/21/2024

Version Issued Date: