Lifileucel (AMTAGVI®) is a treatment for patients with previously treated inoperable or metastatic melanoma. Through autologous tumour-infiltrating lymphocyte therapy, in which T-cells are isolated from patients’ tissue, expanded ex vivo, and reinfused, the goal is to trigger an anti-tumour response. The US Food and Drug Administration (FDA) approved lifileucel in February 2024 for patients with inoperable or metastatic melanoma who had previously received an anti-PD-1 therapy and, in case of BRAF-V600 positivity, BRAF inhibitors (with or without MEK inhibitors).

The efficacy and safety of lifileucel were investigated in a single-arm phase 2 multi-cohort study. The pooled analysis of two cohorts showed a complete response rate of 5%, a partial response rate of 26%, and a stable disease rate of 46%. Additional results include an objective response rate of 31.4%, a median overall survival of 13.9 months, and a progression-free survival of 4.1 months. Regarding safety, all patients experienced at least one treatment-related adverse event, with thrombocytopenia (76.9%), anaemia (50.0%), and febrile neutropenia (41.7%) being the most frequently observed. Six patients died within 30 days after lifileucel infusion.

Lifileucel represents an option for heavily pre-treated patients; however, there are currently no studies that directly compare lifileucel with other therapies. The absence of a specialised melanoma registry also reinforces the existing evidence gap. Additionally, treatment with lifileucel is associated with high costs and structural challenges (production of cell therapy as well as equipment for specialised centres).