Vitiligo-like hypopigmentation secondary to adjuvant checkpoint inhibitor therapy in patients with resectable stage III melanoma: a cohort from two tertiary hospitals.

Abstract

Vitiligo-like hypopigmentation induced by immune checkpoint inhibitors (ICIs) has been largely associated with improved survival outcomes in metastatic melanoma. However, its development during adjuvant ICI therapy and its role as a prognostic factor in this setting remain unclear. We aimed to describe ICI-induced vitiligo in a cohort of patients with resected stage III melanoma treated with adjuvant ICI and to identify differences in progression-free survival (PFS) and distant metastasis-free survival (DMFS) between those who developed vitiligo and those who did not. Patients and data were collected from two institutions, both retrospectively and prospectively, from January 2018 to February 2024. Patients were divided into 'vitiligo' and 'non-vitiligo' groups for comparisons. Of 40 patients, 22.5% developed ICI-induced vitiligo [median follow-up: 23 months (1-73)]. Treatments received were nivolumab (70%) and pembrolizumab (30%). Fifty-five percent of the patients completed 1 year of treatment, 37.5% discontinued and 7.5% were still ongoing. Vitiligo and non-vitiligo groups differed in the cause of treatment discontinuation (severe toxicity in vitiligo vs. progression in non-vitiligo, P  = 0.005) and the occurrence of progression (none in vitiligo vs. 52% in non-vitiligo, P  = 0.001). Survival analyses showed longer PFS in vitiligo group ( P  = 0.013) and no differences in DMFS ( P  = 0.111). ICI-induced vitiligo typically affected photo-exposed areas, with a median time to onset of 4 months (1-27). These preliminary results on ICI-induced vitiligo in adjuvant treatment are in agreement with those reported in advanced melanoma treatment, so its development in the adjuvant setting could be a sign of good prognosis as well.