Can immunological phenotype predict response after isolated limb perfusion for patients with in-transit metastasis of melanoma?

Abstract Introduction Isolated limb perfusion (ILP) is a regional treatment for patients with melanoma in-transit metastases (ITM) confined to extremities, using a high dose of melphalan. ILP has a high response rate, with approximately 60% having a complete response (CR). This study aimed to validate if pre-operative immunological phenotype could be a predictive factor for CR after ILP. Method A total of 132 patients with melanoma in-transit metastases treated with first-time ILP between January 2012 and March 2023 were included. All patients had to have an available pre-operative clinical blood sample needed for fluorescence activated cell sorting (FACS) analysis. Predictive clinical and immunological factors for CR after ILP were analyzed using univariable and multivariable analysis. Response was evaluated using RECIST 1.1 criteria modified for cutaneous lesions. Result Out of the 132 patients, response was evaluable in 119 (90%) and 53% achieved a CR. Immunological factors significantly and independently associated with an CR after ILP, adjusted for age, sex, number of metastases and largest metastases, were percentage of CD3+8+ cells (OR 1.07, CI 95% 1.02-1.13, p=0.012) and percentage of CD3+8+45RA+ cells (OR 1.11, CI 95% 1.01-1.22, p=0.029). Discussion Immunological phenotype described as percentage of cytotoxic T-cells and naïve cytotoxic T-cells are together with tumor burden important predictive factors for response after ILP for patients with melanoma ITM. This could potentially contribute to better patient selection and individualized treatment algorithms but might also be a foundation for future novel treatment combinations, where an ongoing trial is currently combining ILP with a PD-1 inhibitor (ClinicalTrials.gov NCT03685890).