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

ESMO Open

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M. Guida¹  S. Strippoli¹  M. Maule²  P. Quaglino³  A. Ramondetta³  V. Chiaron Sileni⁴  G. Antonini Cappellini⁵  P. Queirolo⁶  L. Ridolfi⁷  M. Del Vecchio⁸  E. Cocorocchio⁹  A.M. Di Giacomo^1,10  L. Festino^1,11  B. Merelli^1,12  M. Occelli^1,13  S. Brugnara^1,14  A. Minisini^1,15  S. Sava^1,16  S. Tommasi^1,17  S. De Summa^1,17 

[1] Rare Tumors and Melanoma Unit, IRCCS Istituto Tumori ‘Giovanni Paolo II’;Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin;Dermatologic Clinic, Department of Medical Sciences, University of Turin Medical School;Veneto Institute of Oncology IOV-IRCCS;Department of Oncology and Dermatological Oncology;Skin Cancer Unit, IRCCS Ospedale Policlinico San Martino;Medical Oncology Department, IRCCS National Cancer Research Centre;Medical Oncology Unit, Department of Medical Oncology and Hematology;Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCS;Center for Immuno-Oncology University Hospital of Siena;Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale;Department of Medical Oncology;Department of Medicine, Clinical Oncology and Translational Research, Azienda Ospedaliera Santa Croce and Carle University Teaching Hospital;Oncology Unit, S. Chiara Hospital;Department of Oncology, ASUIUD University Hospital of Udine;Medical Oncology Unit, A.O. Papardo & Department of Human Pathology, University of Messina;Molecular Diagnostic and Pharmacogenetics Laboratory, IRCCS Istituto Tumori ‘Giovanni Paolo II’

关键词: melanoma;    immunotherapy;    vitiligo;    checkpoint inhibitors;    white blood cells;    monocytes;    immune-related toxicity;   

DOI  :  10.1016/j.esmoop.2021.100064

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

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.

【 授权许可】

CC BY|CC BY-NC-ND