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

M Guida; S Strippoli; M Maule; P Quaglino; A Ramondetta; V Chiaron Sileni; G Antonini Cappellini; P Queirolo; L Ridolfi; M Del Vecchio; E Cocorocchio; A M Di Giacomo; L Festino; B Merelli; M Occelli; S Brugnara; A Minisini; S Sava; S Tommasi; S De Summa; Italian Melanoma Intergroup

doi:10.1016/j.esmoop.2021.100064

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

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

Authors

M Guida¹, S Strippoli², M Maule³, P Quaglino⁴, A Ramondetta⁴, V Chiaron Sileni⁵, G Antonini Cappellini⁶, P Queirolo⁷, L Ridolfi⁸, M Del Vecchio⁹, E Cocorocchio¹⁰, A M Di Giacomo¹¹, L Festino¹², B Merelli¹³, M Occelli¹⁴, S Brugnara¹⁵, A Minisini¹⁶, S Sava¹⁷, S Tommasi¹⁸, S De Summa¹⁸; Italian Melanoma Intergroup

Affiliations

¹ Rare Tumors and Melanoma Unit, IRCCS Istituto Tumori 'Giovanni Paolo II', Bari, Italy. Electronic address: micguida57@gmal.com.
² Rare Tumors and Melanoma Unit, IRCCS Istituto Tumori 'Giovanni Paolo II', Bari, Italy.
³ Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy.
⁴ Dermatologic Clinic, Department of Medical Sciences, University of Turin Medical School, Turin, Italy.
⁵ Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
⁶ Department of Oncology and Dermatological Oncology, IDI-IRCCS, Rome, Italy.
⁷ Skin Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
⁸ Medical Oncology Department, IRCCS National Cancer Research Centre, Meldola (FO), Italy.
⁹ Medical Oncology Unit, Department of Medical Oncology and Hematology, Fondazione IRCCS, Milan, Italy.
¹⁰ Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy.
¹¹ Center for Immuno-Oncology University Hospital of Siena, Siena, Italy.
¹² Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale, Naples, Italy.
¹³ Department of Medical Oncology, ASST Papa Giovanni XXIII, Bergamo, Italy.
¹⁴ Department of Medicine, Clinical Oncology and Translational Research, Azienda Ospedaliera Santa Croce and Carle University Teaching Hospital, Cuneo, Italy.
¹⁵ Oncology Unit, S. Chiara Hospital, Trento, Italy.
¹⁶ Department of Oncology, ASUIUD University Hospital of Udine, Udine, Italy.
¹⁷ Medical Oncology Unit, A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy.
¹⁸ Molecular Diagnostic and Pharmacogenetics Laboratory, IRCCS Istituto Tumori 'Giovanni Paolo II', Bari, Italy.

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.

Publication types

Observational Study

MeSH terms

Aged
Female
Humans
Immune Checkpoint Inhibitors / adverse effects*
Immune Checkpoint Inhibitors / therapeutic use
Ipilimumab / adverse effects*
Ipilimumab / therapeutic use
Italy / epidemiology
Male
Melanoma* / drug therapy
Vitiligo* / chemically induced
Vitiligo* / diagnosis

Substances

Immune Checkpoint Inhibitors
Ipilimumab