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

[BACKGROUND] Isolated limb perfusion (ILP) is a regional treatment for patients with melanoma in-transit metastases (ITM) confined to extremities. Reported complete response (CR) rates for ILP varies but is approximately 50-70 %. This study aims to analyze if specific immunological phenotypes could predict CR after ILP.

[METHODS] 132 patients undergoing ILP as a first treatment for melanoma ITM between January 2012 and March 2023 were included. The number and percentage of naïve and memory T and B cell subtypes, and natural killer (NK) cells, were characterized by analyzing pre-operative blood sample using fluorescence activated cell sorting (FACS). Predictive clinical and immunological factors for CR after ILP were analysed using univariable and multivariable analysis.

[RESULTS] Response was evaluable in 119 patients (90 %), of which 53 % achieved a CR. After adjusting for age, sex, number of metastases and size of the largest metastasis, immunological factors independently associated with a CR, were percentage of cytotoxic T cells (CD38) (OR 1.07, 95 % CI 1.02-1.13, p = 0.012) and percentage of naive cytotoxic T cells (CD3845RA) (OR 1.11 95 % CI 1.01-1.22, p = 0.029).

[CONCLUSION] 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 contribute to better patient selection, individualized treatment algorithms and be a foundation for further research into systemic immunological effects of regional cancer therapies. This includes novel treatment combinations, where an ongoing trial is currently combining ILP with a PD-1 inhibitor (ClinicalTrials.gov NCT03685890).