Multicenter cohort study of association of specific cutaneous irAEs with durable response to immune checkpoint blockade in metastatic melanoma

Immune checkpoint blockade (ICB) improved survival outcomes of patients with metastatic melanoma. Yet up to 65% of patients experience primary resistance and nearly half of initial responders acquire resistance. A pivotal challenge is to identify markers to predict durable ICB responses. A retrospective multicenter study in Germany, including 741 patients diagnosed with non-resectable stage III/IV melanoma who were treated with ICB between April 2012 and August 2025, evaluated the association of specific types of cutaneous immune-related adverse events (irAEs) and clinical ICB benefit. Among these patients, 221 (29.7%) developed cutaneous irAEs within the median follow-up period of 48 months. Among these patients, tumor recurrences were observed in 17.2% of patients with poliosis, 57.7% of patients with vitiligo, and 60.9% of patients with other cutaenous irAEs. In line, in these three groups the objective response rate was 93.1% versus 58.8% versus 38.8% (p<0.001), the median progression-free survival was not reached versus 31 months versus 9 months (p<0.001), and the median overall survival was Not reached versus not reached versus 69 months (p<0.001). In poliosis patients, enhanced tumor control was seen regardless of initial tumor burden, treatment duration, of the presence of melanoma brain metastases. While other irAEs usually arise early on ICB start, poliosis was a late event that occurred at a median of 6 months. The authors conclude that this study identified poliosis as a distinct marker linked to strong and durable ICB responses (graphical abstract).