Isolated Limb Infusion/Perfusion for Unresectable Acral Versus Non-Acral Melanoma In-Transit Metastases

BackgroundAcral lentiginous melanoma (ALM) has a worse prognosis than non-ALM subtypes and poorly understood genetic profile, limiting therapy options. This study compares outcomes of isolated limb infusion or perfusion (ILI/ILP) in patients with ALM or non-ALM.MethodsA multi-institution retrospective review including patients with unresectable melanoma in-transit metastases (ITM) treated with ILI/ILP from 2002 to 2023.ResultsA total of 364 patients were identified: 55% female; median age 71 years; 84 with ALM; 280 non-ALM. Acral lentiginous melanoma tumors had deeper Breslow thickness (4 mm vs. 2.9 mm, P = .005) and more frequent ulceration (38% vs. 27%, P = .03). On multivariable analysis, there were no differences in complete or overall response rates between ALM vs. non-ALM. Median follow-up was 3 years. On Kaplan-Meier analysis, median progression-free survival (PFS) was shorter for ALM (5.6 vs. 7.7 months, P = .02). Out-of-field PFS was shorter for ALM (9.6 vs. 15.3 months, P = .02). Disease-specific survival was shorter for ALM (3.5 vs. 7.8 years, P = .008). In-field PFS and overall survival were not different for ALM vs. non-ALM. On multivariable analysis, there were no differences in PFS (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.0-1.74; P = .05) or in-field PFS (HR 1.25, 95% CI 0.95-1.65; P = .1). Out-of-field PFS remained shorter for ALM (HR 1.44, 95% CI 1.09-1.91; P = .01).ConclusionsIsolated limb infusion or perfusion is equally effective in achieving locoregional disease control in patients with ALM or non-ALM ITM. Disease-specific survival and out-of-field PFS were significantly shorter with ALM, likely reflective of ALM's more aggressive biology, and highlights a potential opportunity for systemic therapy with ILI/ILP to optimize local and distant disease control.