Background

Amtagvi is a tumor-derived autologous T cell immunotherapy indicated for the treatment of unresectable or metastatic melanoma in adults who have been previously treated with a programmed death receptor-1 (PD-1) blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. It is manufactured from resected patient tumor tissue from one or more tumor lesions and is composed primarily of T cells of the CD4+ and CD8+ T cell lineages. Prior to infusion, the patient should be treated with lymphodepleting chemotherapy consisting of cyclophosphamide followed by fludarabine. Amtagvi is administered between 24 hours and 4 days after completion of lymphodepleting chemotherapy. After completion of the Amtagvi infusion, IV interleukin-2 (IL-2), given as Proleukin®‡ (aldesleukin IV infusion) is administered for up to 6 doses (dosed every 8-12 hours) to support cell expansion in vivo. Treatment must occur at a treatment center certified by the manufacturer. There are boxed warnings in the label for this product for treatment-related mortality, prolonged severe cytopenia, cardiac disorders, respiratory failure, and acute renal failure.

Melanoma is a relatively common cancer in the U.S. with an estimated 100,640 new cases predicted each year. Invasive melanoma is only approximately 1% of these skin cancers, but it results in the most death. Risk factors for melanoma include sun exposure, male sex, high nevus count, atypical nevi, family and/or personal history, and others. Current primary treatment options for melanoma that has metastasized or cannot be surgically treated include immunotherapy using immune checkpoint inhibitors (such as anti-PD-1/PD-L1 agents) or targeted therapy involving BRAF/MEK inhibitors, particularly if the melanoma carries a BRAF V600 mutation. For patients who do not respond to or experience a relapse after receiving immunotherapy or targeted therapy, alternative immunotherapies or targeted therapies with different mechanisms of action can be considered. In cases of continued disease progression, chemotherapy is an option, but its efficacy is limited, with response rates reported at only 4 to 12% and a relatively short median overall survival rate of 7 months. Amtagvi is the first treatment to be approved for these patients who have progressive disease after immunotherapy and targeted therapy. The National Comprehensive Cancer Network (NCCN) guidelines for cutaneous melanoma (Version 2.2024) recommend consideration of TIL therapy for patients with good performance status who have progressed on anti-PD-1 based therapy and BRAF/MEK inhibition (if BRAF V600 mutation present). These guidelines further state that TIL therapy should not be considered for patients with inadequate cardiac, pulmonary, and/or renal function, poor performance status, or with untreated or active brain metastases.

Policy (Criteria)

Amtagvi may be approved as medically necessary if the following criteria are met: 

1. Individual is 18 years of age or older; AND 

2. Individual has a diagnosis of unresectable or metastatic melanoma; AND 

3. Individual has progressed on a programmed cell death protein-1 (PD-1) blocking antibody and if BRAF V600 mutation-positive, a BRAF inhibitor with or without a MEK inhibitor; AND 

4. Individual has met all the following hematologic parameters:  

1. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3; AND 

2. Hemoglobin (Hb) ≥ 9.0 g/dL; AND 

3. Platelet count ≥ 100,000 cells/mm3; AND 

5. Individual has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; AND 

6. Individual is using as a one-time, single administration treatment for autologous use only. 

References

1. Iovance Biotherapeutics. Amtagvi. Package Insert. Philadelphia, PA 19112. February 2024.
2. Amtagvi Drug Evaluation. Express Scripts. Updated February 2024.
3. FDA Approves First Cellular Therapy to Treat Patients with Unresectable or Metastatic Melanoma. February 16,2024 Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-unresectable-or-metastatic-melanoma#:~:text=Treatment%20for%20unresectable%20or%20metastatic,system%20fight%20off%20cancer%20cellshttps://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-unresectable-or-metastatic-melanoma#:~:text=Treatment%20for%20unresectable%20or%20metastatic,system%20fight%20off%20cancer%20cells opens a dialog window‌.
4. Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma (LN-144). NCT02360579. Available at: https://clinicaltrials.gov/study/NCT02360579. https://clinicaltrials.gov/study/NCT02360579.  opens a dialog window‌
5. Study to Investigate Lifileucel Regimen Plus Pembrolizumab Compared With Pembrolizumab Alone in Participants With Untreated Advanced Melanoma. NCT05727904. Available at: https://clinicaltrials.gov/study/NCT05727904https://clinicaltrials.gov/study/NCT05727904 opens a dialog window‌
6. Amtagvi (lifileucel) New Drug Review. IPD Analytics. February 2024.
7. NCCN Drugs and Biologics Compendium. Amtagvi. Accessed April 5, 2024. Available at: https://www.nccn.org/professionals/drug_compendium/content/https://www.nccn.org/professionals/drug_compendium/content/ opens a dialog window‌ 

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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