Pathological Response and Toxicity of Neoadjuvant Immunotherapy in Advanced Melanoma

To evaluate pathological response and safety outcomes of neoadjuvant immunotherapy in a real-world cohort of patients with locally advanced resectable melanoma.

A retrospective chart review was conducted on 24 consecutive patients treated between 2023-2025. Most patients had Stage IIIC disease (14/24, 58%). Treatment comprised pembrolizumab monotherapy (19/24, 79%) or ipilimumab/nivolumab (5/24, 21%). Pathological response was assessed using the International Neoadjuvant Melanoma Consortium criteria, and categorised as complete (pCR), partial (pPR) or no pathological response (pNR).

Overall, 4/24 (16.7%) achieved pCR and 8/24 (33.3%) achieved pPR. In the pembrolizumab subgroup, 4/19 (21%) achieved pCR. NRAS codon 61 mutations were present in 10/24 (42%); among these, 5/10 (50%) achieved pPR and 2/10 (20%) progressed pre-operatively. Adverse events occurred in 11/24 (46%), including 8/19 (42%) on pembrolizumab and 3/5 (60%) on ipilimumab/nivolumab. Colitis occurred in 2/5 (40%) receiving combination therapy. Four patients (4/24, 16.7%) died due to disease progression.

Observed pCR rates with pembrolizumab align with controlled trial data, supporting the applicability of neoadjuvant therapy. The high prevalence of NRAS mutations and associated pPR is notable, though progression in a subset underscores the need for improved biomarker-guided treatment selection. Toxicity, particularly colitis with combination therapy, remains a significant clinical challenge.