Supplementary file 1_Does tumor-infiltrating lymphocyte therapy improve survival outcomes in patients with advanced melanoma?.docx

Metastatic melanoma is an aggressive form of cancer, with poor patient outcomes when first-line treatments fail. Success has been seen in checkpoint blockade immunotherapies such as anti-PD-1 and anti-CTLA4 treatments, however long-term use results in resistance. Tumor-infiltrating lymphocyte (TIL) therapy is effective in treating melanoma as a second-line option, particularly in cancers such as melanoma, breast and ovarian cancer. With the 2024 FDA approval of Iifileucel (Amtagvi), a type of TIL therapy, this literature review aims to establish how effectively TIL therapy can treat metastatic and advanced melanomas, to evaluate if this type of therapy should be approved in the UK. A detailed search of databases Medline and Cochrane Library was conducted using terms related to “tumor-infiltrating lymphocyte therapy” and “advanced melanoma” focusing on peer-reviewed research and phase II/III clinical trials published between 2015 and 2025. Studies were included if written in English and reported survival-related outcomes. The evidence highlights TIL therapy as an effective treatment for late-stage melanoma, with up to 20% of patients showing complete responses and all studies regarding TIL therapy as equally effective or more successful than the control drugs used. However, some studies reported adverse effects, mostly linked to lymphodepleting chemotherapy. Overall, the literature indicates that TIL therapy is a breakthrough drug that could change the treatment of melanoma, and allow patients another, effective treatment option, after first-line treatments are no longer suitable. This review concludes that future research should focus on larger cohort studies, and cost-effectiveness investigations to support approval in the UK.