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Observational Study
. 2021 Apr;6(2):100064.
doi: 10.1016/j.esmoop.2021.100064. Epub 2021 Mar 10.

Immune checkpoint inhibitor associated vitiligo and its impact on survival in patients with metastatic melanoma: an Italian Melanoma Intergroup study

M Guida  1 , S Strippoli  2 , M Maule  3 , P Quaglino  4 , A Ramondetta  4 , V Chiaron Sileni  5 , G Antonini Cappellini  6 , P Queirolo  7 , L Ridolfi  8 , M Del Vecchio  9 , E Cocorocchio  10 , A M Di Giacomo  11 , L Festino  12 , B Merelli  13 , M Occelli  14 , S Brugnara  15 , A Minisini  16 , S Sava  17 , S Tommasi  18 , S De Summa  18 ; Italian Melanoma Intergroup
Affiliations
Observational Study

Immune checkpoint inhibitor associated vitiligo and its impact on survival in patients with metastatic melanoma: an Italian Melanoma Intergroup study

M Guida et al. ESMO Open. 2021 Apr.

Abstract

Background: Checkpoint inhibitors in melanoma can lead to self-immune side-effects such as vitiligo-like depigmentation (VLD). Beyond the reported association with favorable prognosis, there are limited data regarding VLD patient features and their echo on the therapeutic outcomes.

Methods: To assess the association between VLD and a series of clinical and biological features as well as therapeutic outcomes, we built an observational cohort study by recruiting patients who developed VLD during checkpoint inhibitors.

Results: A total of 148 patients from 15 centers (101 men, median age 66 years, BRAF mutated 23%, M1c 42%, Eastern Cooperative Oncology Group (ECOG) status 0/1 99%, normal lactate dehydrogenase 74%) were enrolled. VLD was induced by ipilimumab, programmed cell death-1 (PD-1) inhibitors, and their combination in 32%, 56%, and 12%, respectively. The median onset was 26 weeks and it was associated with other skin and nonskin toxicities in 27% and 28%, respectively. After 3 years of VLD onset, 52% (95% confidence interval 39% to 63%) were progression free and 82% (95% confidence interval 70% to 89%) were still alive. The overall response rate was 73% with 26% complete response. Univariable analysis indicated that BRAF V600 mutation was associated with a better overall survival (P = 0.028), while in multivariable analysis a longer progression-free survival was associated with BRAF V600 (P = 0.093), female sex (P = 0.008), and M stage other than 1a (P = 0.024). When VLD occurred, there was a significant decrease of white blood cell (WBC) count (P = 0.05) and derived WBC-to-lymphocytes ratio (dWLR; P = 0.003). A lower monocyte count (P = 0.02) and dWLR (P = 0.01) were also reported in responder patients.

Conclusions: Among VLD population, some features might help to identify patients with an effective response to immunotherapy, allowing clinicians to make more appropriate choices in terms of therapeutic options and duration.

Keywords: checkpoint inhibitors; immune-related toxicity; immunotherapy; melanoma; monocytes; vitiligo; white blood cells.

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Conflict of interest statement

Disclosure The authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier curves of (A) progression-free survival and (B) overall survival (OS) in the entire population of 148 patients developing vitiligo-like depigmentation (VLD) during treatment with checkpoint inhibitors. (C) OS by BRAF status (P = 0.028).
Figure 2
Figure 2
(A) Boxplots showing a significant variation of absolute value of white blood cells (WBCs) and WBC to lymphocytes ratio between the beginning of immunotherapy and the vitiligo-like depigmentation onset. (B) At those time-points, a lower monocyte count (P = 0.02) and dWLR were reported in responder versus nonresponder patients.
See this image and copyright information in PMC

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