Camille Hua1, Lise Boussemart1, Christine Mateus1, Emilie Routier1, Céline Boutros1, Hugo Cazenave1, Roxane Viollet1, Marina Thomas1, Séverine Roy1, Naima Benannoune1, Gorana Tomasic2, Jean-Charles Soria3, Stéphane Champiat4, Matthieu Texier5, Emilie Lanoy5, Caroline Robert6. 1. Department of Dermatology, Cancer Campus, Gustave Roussy Institute, Villejuif, France. 2. Department of Pathology, Cancer Campus, Gustave Roussy Institute, Villejuif, France. 3. Department of Early Clinical Development, Cancer Campus, Gustave Roussy Institute, Villejuif, France4Paris-Sud University, Grand Paris, France. 4. Department of Early Clinical Development, Cancer Campus, Gustave Roussy Institute, Villejuif, France5Institut National de la Santé et de la Recherche Médicale U 981, Cancer Campus, Gustave Roussy Institute, Grand Paris, France. 5. Biostatistics and Epidemiology Unit, Gustave-Roussy Institute, Villejuif, France7Centre de recherche en épidémiologie et Santé des populations, Institut National de la Santé et de la recherche médicale, Université Paris-Sud, Université de Versailles Saint. 6. Department of Dermatology, Cancer Campus, Gustave Roussy Institute, Villejuif, France5Institut National de la Santé et de la Recherche Médicale U 981, Cancer Campus, Gustave Roussy Institute, Grand Paris, France.
Abstract
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.
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.
Authors: Biagio Ricciuti; Carlo Genova; Andrea De Giglio; Maria Bassanelli; Maria Giovanna Dal Bello; Giulio Metro; Marta Brambilla; Sara Baglivo; Francesco Grossi; Rita Chiari Journal: J Cancer Res Clin Oncol Date: 2018-12-01 Impact factor: 4.553
Authors: Charles Kyung Min Lee; Shufeng Li; Duy Cong Tran; Gefei Alex Zhu; Jinah Kim; Bernice Y Kwong; Anne Lynn S Chang Journal: J Am Acad Dermatol Date: 2018-05-29 Impact factor: 11.527
Authors: Pradnya D Patil; Anthony P Fernandez; Vamsidhar Velcheti; Ahmad Tarhini; Pauline Funchain; Brian Rini; Mohamad Khasawneh; Nathan A Pennell Journal: Oncologist Date: 2018-10-24
Authors: M Xipell; I Victoria; V Hoffmann; J Villarreal; A García-Herrera; O Reig; L Rodas; M Blasco; E Poch; B Mellado; L F Quintana Journal: Oncoimmunology Date: 2018-03-26 Impact factor: 8.110