Immunological phenotype as a predictor for response after isolated limb perfusion for patients with melanoma in-transit metastasis.

Abstract

9565 Background: 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. Methods: A total of 132 patients undergoing ILP as a first treatment for melanoma ITM between January 2012 and March 2023 were included in this study. The number and percentage of naïve and memory T and B cell subtypes, as well as natural killer (NK) cells were characterized by analyzing pre-operative blood samples using fluorescence activated cell sorting (FACS). Univariable and multivariable analysis were used to investigate if any of these subtypes were predictive for response after ILP. Results: Out of the 132 patients included in the study, 53% achieved a CR. Immunological and clinical factors significantly and independently associated with an CR after ILP were: number of metastases (OR 0.98, 95% CI 0.97-1.00, p=0.036), size of largest metastases (OR 0.96, 95% CI 0.93-0.99, p=0.009), 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). Conclusions: 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 in-transit metastasis. 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).