Abstract
Background
Immune checkpoint blockade (ICB) improved survival outcomes for patients with metastatic melanoma. Yet up to 65% of patients experience primary resistance and nearly half of initial responders acquire resistance. The clinical utility of ICB is further tempered by frequent immune-related adverse events (irAEs), which increase in severity and frequency with prolonged treatment duration. Hence, a pivotal challenge is to identify clinically accessible markers to predict durable ICB responses. While prior reports indicate that the development of cutaneous irAEs may reflect robust antitumor immune responses, there is limited evidence linking specific types of cutaneous irAEs to clinical ICB benefit.
Methods
In this retrospective multicenter study, we investigated a cohort of 741 patients diagnosed with non-resectable stage III/IV melanoma who were treated with ICB between April 2012 and August 2025. Patient demographics, tumor characteristics, treatment regimens and survival outcomes were collected within six German skin cancer centers. We stratified patients by the type of cutaneous AE into such with whitening of the body skin (vitiligo), hair (poliosis) or other cutaneous AE. Primary endpoints included progression-free survival (PFS) and objective response rates (ORR).
Results
Among 741 eligible patients, 221 developed cutaneous irAE within the median follow-up period of 48 months. Thereof, we observed tumor recurrences in 17.2% of patients with poliosis, 57.7% of patients developing vitiligo and 60.0% of patients with other cutaneous irAE. In line, we detected a significantly enhanced ORR (93.1% vs 58.8% vs 38.8%, p
0.001), prolonged PFS (Not reached, NR, vs 31 months vs 9 months, p
0.001) and overall survival (NR vs NR vs 69 months, p
Conclusions
Our study identifies poliosis as a distinct and immunologically-informed marker linked to strong and durable ICB responses easily applicable in a routine clinical setting. Detection of poliosis may complement radiographic imaging for clinical decision-making on ICB treatment duration and early cessation and provides a window for translational investigations harnessing epitope-specific T-cell responses to melanoma antigens.