CurrentBlue Cross Blue Shield - IowaPolicy 05.05.33

Amtagvi (tumor-infiltrating lymphocyte therapy) for unresectable or metastatic melanoma

Defines prior authorization coverage criteria, required documentation, clinical and laboratory thresholds, dosing limits, and billing codes for Amtagvi for adult members with unresectable or metastatic melanoma previously treated with a PD-1 inhibitor (and BRAF inhibitor if BRAF V600 mutation-positive). Applies to Wellmark Blue Cross and Blue Shield products subject to member benefit verification.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyAmtagvi (tumor-infiltrating lymphocyte therapy) for unresectable or metastatic melanoma

Policy CodePolicy 05.05.33

Change TypeNo material change

Effective DateApr 24, 2024

Next Review Date

Key ActionSubmit chart notes, labs, and documentation of prior therapies and required clinical parameters to initiate prior authorization review; authorization may be granted for 3 months when criteria are met.

SourceLink

POLICY UPDATE CHANGES

No material clinical/coverage changes — policy remains aligned to FDA labeling and existing criteria.

1Lifetime treatments allowed

3 monthsInitial authorization duration

18+Minimum age (years)

YesPrior PD-1 therapy required

Coverage Summary

Amtagvi is covered with criteria for adults (>= 18 years) with unresectable or metastatic melanoma who have previously been treated with a PD‑1 blocking antibody and, if BRAF V600 mutation‑positive, a BRAF inhibitor (with or without a MEK inhibitor), consistent with the FDA indication and policy criteria. Authorization for treatment may be granted for 3 months when all criteria are met. Approvals are limited to one treatment per lifetime; repeat treatments are considered investigational and are not covered.

Thresholds summary

Lifetime treatments allowed1

Initial authorization duration3 months

Age eligibility18+ years

Prior PD-1 therapy requiredYes

Initial Therapy Criteria — Melanoma

Initial Authorization — Melanoma

Authorization of 3 months may be granted for treatment of unresectable or metastatic melanoma in members 18 years and older when all of the following criteria are met:

ALL of the following

Member is 18 years or older
History of prior treatment with a PD-1 blocking antibody (e.g., pembrolizumab [Keytruda], nivolumab [Opdivo])
If BRAF V600 mutation positive
- Member has received a BRAF inhibitor (e.g., Braftovi, Tafinlar, Zelboraf) with or without a MEK inhibitor (e.g., Cotellic, Mekinist, Mektovi)
Exclusionary melanoma subtypes/conditions (member must NOT have any of the following)

Continuation of Therapy and Dosing Limits

Continuation of Therapy

Policy position on repeat treatment

Repeat treatment of Amtagvi for any indication is considered investigational; safety and efficacy beyond one dose have not been studied and evidence is insufficient to determine effects on net health outcomes

Dosing Limits

Approvals are limited to one treatment per lifetime

Billing Rule

Lifetime dosing limit

Amtagvi approvals are limited to one treatment per lifetime; repeat treatments are considered investigational and not covered.

Applicable Codes

Billing / HCPCS / CPT equivalent usedHCPCS

J3590

Unclassified biologics

Provider Actions & Documentation Requirements

Prior Authorization

Prior authorization required

Prior authorization is required. Submit chart notes, medical record documentation or claims history supporting prior lines of therapy, recent labs demonstrating hematologic and organ function parameters, and test results to initiate review. Authorization may be granted for 3 months when the coverage criteria are met.

J3590
Submit chart notes, medical record documentation or claims history supporting prior lines of therapy, recent labs demonstrating hematologic and organ function parameters, and test results.

Documentation Required

Required documentation for prior auth

Provide documentation of prior PD-1 blockade, BRAF inhibitor use if BRAF V600 mutation–positive, laboratory values demonstrating hematologic and organ function (including ANC, hemoglobin, platelets, eCrCl, ALT/AST, total bilirubin, LVEF, FEV1), ECOG performance status (0–1), lesion size post-resection (≥1.5 cm), and absence of excluded conditions (uveal/ocular melanoma, symptomatic or untreated brain metastases, clinically significant active infection, disallowed organ allograft or prior cell transfer).

Clinical Evidence & References

Key evidence sources: Amtagvi package insert, February 2024 (FDA package insert) and the clinical review article “Tumor‑Infiltrating Lymphocyte Therapy, Metastatic Melanoma,” J Clin Oncol. 2021. The policy aligns coverage with FDA labeling and evidence‑based guidelines/standards of medical practice per the policy background.

Background & Definitions

Amtagvi is a tumor‑infiltrating lymphocyte (TIL) autologous cellular immunotherapy approved by the FDA for adults with unresectable or metastatic melanoma previously treated with a PD‑1 blocking antibody and, if BRAF V600 mutation‑positive, a BRAF inhibitor with or without a MEK inhibitor. The policy aligns coverage with product labeling and evidence‑based guidelines and requires submission of documentation of prior PD‑1 (and BRAF inhibitor when applicable) therapy, recent laboratory results demonstrating adequate and stable organ function, and hematologic parameters meeting specified thresholds.

Term	Definition
Amtagvi
Tumor-infiltrating lymphocyte (TIL) autologous cellular immunotherapy product indicated for treatment of unresectable or metastatic melanoma as specified in FDA labeling.
PD-1 blocking antibody
Programmed death-1 receptor inhibitors such as pembrolizumab (Keytruda) and nivolumab (Opdivo).

Revision History

2024-04-24Effective

Policy original effective date (policy #05.05.33).

2025-08-01Last reviewLatest

Most recent policy review date.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyAmtagvi (tumor-infiltrating lymphocyte therapy) for unresectable or metastatic melanoma

Policy CodePolicy 05.05.33

Change TypeNo material change

Effective DateApr 24, 2024

Next Review Date

SourceLink

On This Page

Uveal or ocular melanoma

Symptomatic and/or untreated brain metastases

Clinically significant active infection

Organ allograft (except kidney transplant) or prior cell transfer

Hematologic parameter requirements (member must meet ALL)

Absolute neutrophil count (ANC) >= 1000/mm3>= 1000/mm3
Hemoglobin (Hb) >= 9.0 g/dL>= 9.0 g/dL
Platelets >= 100,000/mm3>= 100,000/mm3

Organ function and performance status (member must meet ALL)

Estimated creatinine clearance (eCrCl) >= 40 mL/min using Cockcroft-Gault formula>= 40 mL/min
Serum ALT and AST < 3 x ULN; patients with liver metastasis < 5 x ULN< 3 x ULN (or < 5 x ULN with liver metastasis)
Total bilirubin < 2 mg/dL except patients with Gilbert-Meulengracht syndrome; in those patients total bilirubin may be <= 3.0 x ULN< 2 mg/dL (exception: Gilbert-Meulengracht up to 3.0 x ULN)
Left ventricular ejection fraction (LVEF) > 45%> 45%
Forced expiratory volume in one second (FEV1) > 60%> 60%
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 10 or 1

Member has at least one resectable lesion (or aggregate of lesions resected) of minimum 1.5 cm in diameter post-resection to generate tumor-infiltrating lymphocyte (TIL)>= 1.5 cm

Member has not previously received tumor-derived autologous T cell immunotherapy (including lifileucel) in their lifetime for the treatment of melanoma

Billing Rule

Lifetime dosing limit

Amtagvi approvals are limited to one treatment per lifetime; repeat treatments are considered investigational and not covered.

J3590