TIL therapy shows durable responses in refractory melanoma as adoption expands

Tumour-infiltrating lymphocyte (TIL) therapy offers the potential for durable clinical benefit in select patients with advanced melanoma, especially after progression on treatment with immune checkpoint inhibitors and/or targeted therapies. The 2024 FDA approval of Lifileucel (Amtagvi), a commercially manufactured autologous TIL product, marked a key milestone in integrating advanced therapy medicinal products into routine care for solid tumours.

Metastatic melanoma has long been one of the most challenging malignancies to treat, largely due to its resistance to traditional chemotherapy and radiation. Once it is metastatic, there have been very limited options, and immunotherapeutic approaches give responses in 5% to 10% of patients.

TIL therapy is a different modality of immunotherapy. In patients with advanced melanoma refractory to anti-PD-1 immunotherapy and, in the setting of BRAF V600 positivity, targeted therapy, the phase II C-144-01 study demonstrated an initial objective response rate of 31.4%. TIL therapy gives deep, durable responses in one-third of patients, and sustained remissions beyond 4 years in up to 10% of patients.

Further follow up at five years confirmed durability of responses in 31.3% of treated patients with a median duration of response of 36.5 months, and several responses deepened over time. In contrast, best estimates of durability of response with combination immunotherapy after previous anti-PD-1 exposure approximate 6-16.6 months, despite relative equivalence in the rate of initial responses.

TIL therapy is a complex process, involving tumour harvest, TIL isolation and expansion, pre-infusion non-myeloablative lymphodepletion chemotherapy, and post-infusion high-dose interleukin-2 to support in vivo survival and/or expansion of infused cells. The treatment requires complex coordination, including patient selection, tumour procurement, manufacturing logistics, lymphodepletion, and IL-2 administration, all contingent on specialised infrastructure and well-considered integrated care pathways.

Health Canada has approved Lifileucel, with regulatory and funding decisions across the United Kingdom and Europe still pending. TIL therapy is currently under review by regulators and funding bodies outside of the United States and Canada, including the Medicines and Healthcare products Regulatory Agency and the European Medicines Agency, both of which anticipate publishing decisions in 2026. A nationally coordinated effort is required to harmonise clinical prioritisation strategies, maintain oversight by multidisciplinary specialist tumour boards, and consider investment in future-proof decentralised manufacturing capacity.