Historical evaluation of clinical outcomes and safety following isolated limb perfusion for unresectable melanoma: Real-world data from the Mannheim Cancer Center.

BACKGROUND: In-transit and bulky metastases of cutaneous melanoma represent a therapeutic challenge, particularly when lesions are not amenable to surgical excision. Modern systemic therapies have improved outcomes in advanced melanoma, but local disease progression often persists. Isolated limb perfusion (ILP) can serve as an effective regional salvage approach in patients with therapy-refractory local melanoma metastases when no other treatment options remain, offering the potential to achieve durable local control. OBJECTIVES: The objective of this study was to evaluate clinical responses, progression-free survival (PFS) and safety of ILP as a historical regional cytotoxic salvage therapy, and to exploratorily analyze clinical indicators associated with treatment response in patients with unresectable extremity melanoma metastases within a real-world setting. DESIGN: This study was designed as a retrospective, exploratory, single-center observational cohort study. METHODS: We performed a retrospective single-center analysis of 36 patients with unresectable in-transit or bulky melanoma metastases treated with ILP between 2005 and 2015. Clinical responses, local progression-free survival and safety were evaluated, and potential clinical correlates were exploratorily analyzed. RESULTS: Overall, 72.2% of patients achieved local disease control, including a complete response (CR) rate of 27.8%. Patients with in-transit metastases had significantly longer PFS than those with bulky disease. Female sex, age >65 years, and BRAF mutation were associated with longer local PFS, although these findings should be interpreted cautiously due to small subgroup sizes. Prior systemic therapy did not significantly affect PFS, but patients previously treated with immunotherapy showed a trend toward shorter PFS. Treatment-related toxicity was limited to Wieberdink grade I-III reactions. CONCLUSIONS: ILP remains a valuable palliative salvage option for selected patients with melanoma metastases of the extremities who are refractory to modern systemic therapies. In this setting, ILP can achieve meaningful and durable local disease control with a manageable safety profile while preserving limb function.