Association of Vitiligo With Tumor Response in Patients With Metastatic Melanoma Treated With Pembrolizumab

IMPORTANCE: Vitiligo is an autoimmune skin disorder that reacts against melanocytes. The association of vitiligo with tumor response in patients with melanoma who undergo immunotherapy has been reported but is still controversial. OBJECTIVE: To prospectively evaluate the appearance of vitiligo in pa...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:JAMA dermatology (Chicago, Ill.) Ill.), 2016-01, Vol.152 (1), p.45-51
Hauptverfasser: Hua, Camille, Boussemart, Lise, Mateus, Christine, Routier, Emilie, Boutros, Céline, Cazenave, Hugo, Viollet, Roxane, Thomas, Marina, Roy, Séverine, Benannoune, Naima, Tomasic, Gorana, Soria, Jean-Charles, Champiat, Stéphane, Texier, Matthieu, Lanoy, Emilie, Robert, Caroline
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:IMPORTANCE: Vitiligo is an autoimmune skin disorder that reacts against melanocytes. The association of vitiligo with tumor response in patients with melanoma who undergo immunotherapy has been reported but is still controversial. OBJECTIVE: To prospectively evaluate the appearance of vitiligo in patients receiving pembrolizumab, a monoclonal antibody directed against the programmed death cell receptor. DESIGN, SETTING, AND PARTICIPANTS: This prospective observational study was conducted from January 1, 2012, through September 24, 2013, in a single tertiary care hospital with a unit dedicated to patients with melanoma. Sixty-seven patients with metastatic melanoma who received pembrolizumab treatment in the context of a phase 1 study were included and screened for the emergence of vitiligo. Data were collected from January 1, 2012, to February 28, 2014, and analyzed from February through December 2014. MAIN OUTCOMES AND MEASURES: Objective tumor response with regard to the occurrence of vitiligo in patients receiving pembrolizumab therapy. Correlation between vitiligo occurrence and overall survival was also estimated using the Kaplan-Meier product-limit method and compared with a log-rank test. To prevent guarantee- or lead-time bias, a landmark analysis approach after 12, 16, and 20 weeks of treatment was retained. RESULTS: Of the 67 patients included in the study, 17 (25%) developed vitiligo during pembrolizumab treatment and 50 (75%) did not. An objective (complete or partial) response to treatment was associated with a higher occurrence of vitiligo (12 of 17 [71%] vs 14 of 50 [28%]; P = .002). The time to onset of vitiligo ranged from 52 to 453 (median, 126) days from the start of treatment. Of the 17 patients with vitiligo, 3 (18%) had a complete response, 9 (53%) had a partial response, 3 (18%) had stable disease, and 2 (12%) had progressive disease at the final follow-up. All the patients treated with pembrolizumab who developed vitiligo were alive at the time of analysis, with a median follow-up of 441 days. CONCLUSIONS AND RELEVANCE: Vitiligo, a clinically visible immune-related adverse event could be associated with clinical benefit in the context of pembrolizumab treatment.
ISSN:2168-6068
2168-6084
DOI:10.1001/jamadermatol.2015.2707