CurrentHealth NetPolicy CP PHAR.598

Clinical Policy: Lifileucel (Amtagvi)

Medical necessity and coverage criteria for Amtagvi (lifileucel) for treatment of unresectable or metastatic melanoma previously treated with PD-1 inhibitors; applies to Health Net lines of business including Commercial, HIM, and Medicaid.

Policy Summary

PayerHealth Net

PolicyLifileucel (Amtagvi) — coverage criteria for unresectable or metastatic melanoma

Policy CodePolicy CP PHAR.598

Change TypeMaterial operational additions

Effective Date02.16.24

Next Review Date

Key ActionSubmit prior authorization with documentation of prior PD-1 therapy, lesion resectability/size (≥1.5 cm aggregate), tumor origin, and plan for IL-2 co-administration.

SourceLink

POLICY UPDATE CHANGES

Requirement that Amtagvi be prescribed in combination with IL-2 (aldesleukin) therapy.

Documentation requirement of at least one resectable lesion (or aggregate) minimum 1.5 cm in diameter.

Documentation that melanoma is not of uveal/ocular origin and exclusion for patients with prior organ allograft, prior TIL or CAR-T therapy.

single doseAmtagvi dosing frequency

7.5–72 x10^9viable T cells per dose

72 x10^9maximum viable T cell dose

3 months

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Coverage Criteria — Amtagvi (lifileucel)

Initial Therapy — Melanoma

Covered when ALL of the following are met for unresectable or metastatic melanoma:

Melanoma initial approval criteria: 1) Diagnosis of unresectable or metastatic melanoma; 2) Age >= 18 years; 3) Prescribed by or in consultation with an oncologist; 4) Documentation of disease progression, inadequate response, or intolerance while on anti-PD-1/PD-L1 therapy; 5) If BRAF V600 mutation positive, documentation of prior BRAF inhibitor therapy with or without MEK inhibitor; 6) Amtagvi is prescribed in combination with IL-2 (aldesleukin); 7) Documentation that the member's melanoma is not of known uveal/ocular (ocular) origin; 8) Documentation that the member has at least one resectable lesion (or aggregate of lesions resected) with minimum aggregate diameter >= 1.5 cm; 9) Member has not received a prior organ allograft, prior tumor-infiltrating lymphocyte (TIL) therapy, or prior CAR‑T therapy; 10) Requested dose contains a minimum of 7.5 x 10^9 viable T cells and does not exceed a single administration of 72 x 10^9 viable T cells.dose range 7.5e9-72e9 viable T cells

Approval duration: single dose (one administration); authorization may include up to 6 doses of IL-2 (aldesleukin); all requests require medical director review.

Initial Therapy — detailed initial coverage criteria

Covered when ALL of the following are met for unresectable or metastatic melanoma:

Initial detailed coverage criteria: 1) Diagnosis: unresectable or metastatic melanoma (adult patients); 2) Age >= 18 years; 3) Prescriber: oncologist or in consultation with an oncologist; 4) Prior therapy: documentation of progression, inadequate response, or intolerance to anti-PD-1/PD-L1 therapy; 5) If BRAF V600 mutation–positive: prior BRAF inhibitor with or without MEK inhibitor; 6) Concomitant therapy: Amtagvi must be prescribed in combination with IL-2 (aldesleukin) — note: IL-2 may require prior authorization; 7) Tumor origin: melanoma must not be of known uveal/ocular origin; 8) Tumor tissue: documentation of at least one resectable lesion (or aggregate of lesions resected) with minimum aggregate diameter >= 1.5 cm to allow TIL harvest; 9) Treatment history exclusions: no prior organ allograft and no prior TIL or CAR‑T therapy; 10) Dose requirements: submitted product must contain >= 7.5 x 10^9 viable T cells and the requested administration must not exceed a single dose of 72 x 10^9 viable T cells; 11) Duration/administration: single intravenous administration of lifileucel (Amtagvi); approval duration 3 months (one dose only) with up to 6 doses of IL-2 allowed for supportive therapy; 12) Administrative: provider must submit documentation supporting that member meets all criteria and all requests require medical director review.dose range 7.5e9-72e9 viable T cells

Approval duration: 3 months (one dose only); IL-2 up to 6 doses; medical director review required.

Continued Therapy — Continuation rules

Continuation therapy:

Continued therapy: Amtagvi will not be authorized for continued therapy as it is indicated to be dosed one time only.single administration

Approval duration: Not applicable for continuation; product is a one-time autologous TIL infusion.

Non-FDA–approved indications that are not specifically addressed in this policy are not authorized for coverage unless the provider supplies sufficient off‑label documentation of efficacy and safety in accordance with the applicable off‑label use policies (CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, CP.PMN.53 for Medicaid) or other evidence of coverage documents.

Amtagvi (lifileucel) is indicated to be administered as a single one‑time dose. Requests for additional doses or ongoing repeat administrations beyond this single approved administration are not authorized and are considered not medically necessary.

Coding and Billing References

Informational billing codes referencedCPT/HCPCS

C9399	Unclassified drugs or biologicals
J9999	Not otherwise classified antineoplastic drugs

Minimum lesion size for resection

Minimum aggregate lesion size>= 1.5 cm in diameter (at least one resectable lesion or aggregate)

Context in approval criteriaDocumentation of at least one resectable lesion (or aggregate) >= 1.5 cm in diameter is required for initial Amtagvi approval

Source appendix referenceSee Appendix D / Initial Approval Criteria for resectability and lesion-size documentation

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for requests for Amtagvi and all requests under this policy require medical director review. Providers must submit complete clinical documentation (office notes, labs, pathology, imaging, genetic/mutation testing) supporting that the member meets all approval criteria. Requests for IL-2 (aldesleukin) therapy used in combination with Amtagvi may also require prior authorization per plan rules.

All requests require medical director review
Submit office notes, labs, pathology, imaging, and genetic testing results as applicable
Prior authorization may be required for IL-2 (aldesleukin) therapy

Denial Risk

Requests for Non‑FDA‑Approved Indications

For non-FDA–approved (off-label) indications, provider must include sufficient documentation of efficacy and safety consistent with the applicable off-label use policies (Commercial: CP.CPA.09; Health Insurance Marketplace: HIM.PA.154; Medicaid: CP.PMN.53) or evidence of coverage documents. Requests for non-FDA indications without adequate supporting evidence are at high risk for denial.

Initial Therapy — Detailed Criteria

Initial Therapy — Amtagvi (lifileucel)

Initial coverage criteria for Amtagvi (lifileucel):

Amtagvi (lifileucel) initial criteria: 1) Indication: adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody; 2) If BRAF V600 mutation positive, prior BRAF inhibitor with or without MEK inhibitor; 3) Product dosing: single IV infusion containing between 7.5 x 10^9 and 72 x 10^9 viable T cells (maximum 72 x 10^9); 4) Dose must meet the minimum viable T cell content of 7.5 x 10^9 and not exceed a single administration of 72 x 10^9; 5) Amtagvi must be administered in combination with IL-2 (aldesleukin) per prescriber direction; 6) Other requirements: age >=18, oncologist involvement, documentation of prior PD‑1 therapy failure/progression/intolerance, no prior organ allograft or prior TIL/CAR‑T therapy, tumor not of uveal/ocular origin, and documentation of at least one resectable lesion (or aggregate) >= 1.5 cm to permit TIL harvest.7.5e9-72e9 viable T cells

Single administration; approval duration: 3 months (one dose only); IL-2 up to 6 doses may be authorized; medical director review required.

Continuation Therapy Criteria

Continuation Therapy — ongoing care rules

Continuation/ongoing care rules:

Continuation: Amtagvi is not authorized for continuation therapy because it is indicated to be given as a single administration only; requests for additional doses or ongoing dosing beyond the single approved administration are not medically necessary.single administration

Authorization for supportive IL-2 (aldesleukin) may include up to 6 doses where clinically indicated; prior authorization and medical director review apply.

Step Therapy / Prior Exposure Requirements

Step	Required prior exposure / failure or intolerance
1	Documented progression, inadequate response, or intolerance to anti–PD-1 or anti–PD-L1 therapy (e.g., pembrolizumab, nivolumab) is required prior to Amtagvi (lifileucel) approval.
	If BRAF V600 mutation–positive: prior BRAF inhibitor therapy with or without a MEK inhibitor is required (documented progression, inadequate response, or intolerance).

Quantity Limits

Amtagvi (lifileucel) — quantity limit

Quantity limit1 dose per course (single administration)

Dose range7.5 x 10^9 to 72 x 10^9 viable T cells per single administration

MaximumDoes not exceed a single administration of 72 x 10^9 viable T cells

Aldesleukin (IL-2) — quantity limit

Quantity limitAldesleukin (IL-2) — up to 6 doses per course (authorization may include up to 6 IL-2 doses)

Role in therapyIL-2 is required to be given in combination with Amtagvi to stimulate the infused TIL cells

Prior authorization note

Site of Care and Handling

Note

Product handling and IL‑2 administration setting

Amtagvi is supplied as frozen infusion bag(s) labeled to the specific recipient and requires specialized cellular‑therapy handling and infusion; IL‑2 (aldesleukin) administration is required to stimulate the infused TILs and the IL‑2 setting may require authorization.

Background — Product Overview

Lifileucel (Amtagvi) is an autologous tumor‑infiltrating lymphocyte (TIL) cell therapy manufactured from resected tumor tissue and intended to be given as a one‑time administration. The therapy requires resection of at least one lesion (or an aggregate of lesions) with a minimum aggregate diameter of 1.5 cm to provide adequate tumor tissue for TIL harvesting and ex vivo expansion prior to infusion.

Definitions

IL-2 — definition

DefinitionInterleukin-2 (IL-2): cytokine given after TIL infusion to stimulate the infused tumor-infiltrating lymphocytes

Therapeutic roleAdministered in combination with Amtagvi to promote expansion and activity of the infused TIL product

Authorization noteIL-2 administration may require prior authorization per policy

TIL — definition

DefinitionTumor-infiltrating lymphocytes (TIL): autologous lymphocytes expanded ex vivo from resected tumor tissue for reinfusion

Product relationshipLifileucel (Amtagvi) is an autologous TIL cell therapy derived from resected tumor tissue