Neoadjuvant Immunotherapy Using PD-1 Inhibitors for Resectable Stage III Cutaneous Melanoma-Different Outcomes...

Area of Science:

• Oncology
• Immunotherapy
• Melanoma Research

Background:

• Neoadjuvant immunotherapy is standard for resectable stage III melanoma.
• Real-world data, particularly for in-transit metastasis (ITM), are limited.
• ITM represents a unique challenge in melanoma treatment.

Purpose of the Study:

• To evaluate neoadjuvant immunotherapy efficacy in a population-based cohort of stage III melanoma.
• To specifically assess outcomes for patients with in-transit metastasis (ITM).
• To compare ITM outcomes against lymph node (LN) metastasis and concurrent involvement.

Main Methods:

• Population-based, multicenter observational study of stage III melanoma patients.
• Treatment with neoadjuvant PD-1 inhibitors from 2022-2025 across 5 Swedish academic centers.
• Stratification into LN metastasis only, ITM only, and concurrent LN/ITM groups; primary endpoint: major pathological response (MPR).

Main Results:

• MPR rates were significantly lower in ITM (22%) and concurrent LN/ITM (25%) groups versus LN only (52%).
• Event-free survival (EFS) and locoregional recurrence-free interval (LRFI) were inferior in ITM patients.
• ITM was associated with a 2.00-fold higher risk for EFS events and 4.41-fold higher risk for LRFI events.

Conclusions:

• Neoadjuvant immunotherapy yields lower pathological response in ITM melanoma.
• In-transit metastasis (ITM) is associated with inferior EFS and increased locoregional recurrence risk.
• ITM may represent a distinct phenotype with higher locoregional treatment failure propensity.