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


METHODS
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.


METHODS
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
Vitiligo, a clinically visible immune-related adverse event could be associated with clinical benefit in the context of pembrolizumab treatment.
Department of Dermatology, Cancer Campus, Gustave Roussy Institute, Villejuif, France.
Camille
C
Hua
Department of Dermatology, Cancer Campus, Gustave Roussy Institute, Villejuif, France.
Lise
L
Boussemart
Department of Dermatology, Cancer Campus, Gustave Roussy Institute, Villejuif, France.
Christine
C
Mateus
Department of Dermatology, Cancer Campus, Gustave Roussy Institute, Villejuif, France.
Emilie
E
Routier
Department of Dermatology, Cancer Campus, Gustave Roussy Institute, Villejuif, France.
Céline
C
Boutros
Department of Dermatology, Cancer Campus, Gustave Roussy Institute, Villejuif, France.
Hugo
H
Cazenave
Department of Dermatology, Cancer Campus, Gustave Roussy Institute, Villejuif, France.
Roxane
R
Viollet
Department of Dermatology, Cancer Campus, Gustave Roussy Institute, Villejuif, France.
Marina
M
Thomas
Department of Dermatology, Cancer Campus, Gustave Roussy Institute, Villejuif, France.
Séverine
S
Roy
Department of Dermatology, Cancer Campus, Gustave Roussy Institute, Villejuif, France.
Naima
N
Benannoune
Department of Pathology, Cancer Campus, Gustave Roussy Institute, Villejuif, France.
Gorana
G
Tomasic
Department of Early Clinical Development, Cancer Campus, Gustave Roussy Institute, Villejuif, France4Paris-Sud University, Grand Paris, France.
Jean-Charles
JC
Soria
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.
Stéphane
S
Champiat
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.
Matthieu
M
Texier
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.
Emilie
E
Lanoy
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.
Caroline
C
Robert
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014820:Vitiligo / Q000209:etiology*; D055815:Young Adult
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C582435:pembrolizumab