A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases.

Background: Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC.

Methods: Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM.

Results: A total of 551 patients were treated, with ILI/ILP (n = 356), ICI (n = 125), and TVEC (n = 70) with median follow-up of 5.5 years. Tumor burden was highest with ILI/ILP and lowest with TVEC (p = .002). Breslow thickness was lowest with TVEC (p = .007). TVEC was mostly used in stage IIIB disease versus IIIC for ILI/ILP and ICI (p = .01). Using ICI as the reference category, TVEC had the highest odds of a complete response (CR) (odds ratio, 1.96; p = .029) and a longer local progression-free survival (PFS) (hazard ratio [HR], 0.40; p = .003). ILI/ILP had shorter local PFS (HR, 1.72; p = .012), PFS (HR, 1.79; p < .001), distant metastasis-free survival (DMFS) (HR, 1.75; p = .014), overall survival (HR, 1.82; p = .009), and melanoma-specific survival (HR, 2.29; p = .004). Stage IIIB disease had longer DMFS (HR, 0.24; p < .001) compared to IIIC/D.

Conclusions: TVEC as first-line therapy for unresectable melanoma ITM was associated with superior CR rates and local PFS. Notably, TVEC was used in patients with a lower Breslow thickness, disease stage, and tumor burden. Therefore, when compared to ILI/ILP and ICI, TVEC should be considered as first-line therapy for unresectable stage IIIB melanoma ITM with minimal tumor burden and lower Breslow thickness.