Effects of the Introduction of Modern Immunotherapy on the Outcome of Isolated Limb Perfusion for Melanoma In-Transit Metastases

SIMPLE SUMMARY: Melanoma in-transit metastasis has long been effectively treated with isolated limb perfusion (ILP), a procedure where the limb is treated with high concentrations of heated chemotherapy. The recent treatment revolution with the introduction of modern systemic treatments has changed how metastatic melanoma is treated. We analysed patients treated with ILP before the introduction of systemic immunotherapy (2010–2014) and compared them to those treated after (2017–2021). The patient population is largely unchanged, with only a slight increase in age. Importantly, there was no reduced effect of ILP, also in patients that previously had received and failed immunotherapy, showing that ILP is still a valid and important treatment for patients with melanoma in-transit metastasis. ABSTRACT: Isolated limb perfusion (ILP) is an effective locoregional treatment for melanoma in-transit metastasis, but the advent of modern effective immunotherapy, such as ICI (immune checkpoint inhibitors), has changed the treatment landscape. The primary aims of this study were to compare the characteristics of the patient population receiving ILP before and after the introduction of modern systemic treatments and to assess if outcomes after ILP were influenced by previous immunotherapy treatment. A single-centre analysis of patients that underwent ILP for melanoma in-transit metastasis between 2010 and 2021 was conducted, with patients grouped and compared by treatment time period: pre-ICI era (2010–2014) and ICI era (2017–2021). 218 patients were included. Patients undergoing ILP in the ICI era were slightly older (median age 73 vs. 68 years) compared to the pre-ICI era, with no other difference found. The overall response rate (ORR) was 83% vs. 84% and the complete response (CR) rate was 52% vs. 47% for the pre-ICI era and the ICI era, respectively. For patients that had received and failed immunotherapy prior to ILP (n = 20), the ORR was 75% and the CR rate was 50%. Melanoma-specific survival has improved, with a 3-year survival rate of 54% in the pre-ICI era vs. 86% in the ICI era. The patient population undergoing ILP for in-transit melanoma is largely unchanged in the current era of effective systemic treatments. Response rates have not decreased, and prior ICI treatment did not affect response rates, making ILP still a valid treatment option for this patient group.