Vitiligo Linked to Pembrolizumab Response in Metastatic Melanoma

Vitiligo resulting from treatment with the programmed death-1 inhibitor pembrolizumab correlates with improved response

medwireNews: Development of vitiligo, an autoimmune disorder characterised by hypopigmented skin lesions, is associated with improved response to pembrolizumab in patients with metastatic melanoma, research suggests.

Among 67 patients with unresectable stage III or IV melanoma who were treated with at least three infusions of the anti-programmed death-1 (PD-1) agent in a phase I trial, 25% developed vitiligo, with localised incidence in two patients, generalised in 14 and mixed in the remaining patient. The median time to onset was 126 days.

An objective response was achieved by 71% of patients who developed vitiligo, which was significantly higher than the 28% response rate among those free of vitiligo. Of the responses in the vitiligo group, three were complete and nine were partial, while three patients had stable disease and two progressed.

During a median follow-up of 441 days, there were no deaths among patients who developed vitiligo. But after adjusting for lead-time bias by using a landmark analysis approach, overall survival of patients who developed vitiligo during the initial 12, 16 or 20 weeks was comparable to that of vitiligo-fee patients.

Immune-related adverse events occurred significantly more frequently in patients who did compared with those who did not develop vitiligo, at 76% versus 44%, with dermatological events being particularly common (88 vs 38%).

Moreover, immune-related toxicities of grade 3 or 4 were observed only in melanoma patients who developed vitiligo, with three patients discontinuing treatment as a result.

Vitiligo could be a clinically visible immune-related adverse event associated with clinical benefit in this patient population, say Caroline Robert, from Institute Gustave Roussy in Villejuif, France, and team in JAMA Dermatology.

They caution, however, that “[t]he conclusion that the occurrence of vitiligo might be an early marker of tumor response is difficult to make because the median time to the onset of vitiligo was 126 days and the first radiologic evaluation occurred earlier, after 84 days.”

But the study authors note that in five patients, vitiligo “clearly preceded” the partial response observed at the first radiological assessment.

The team concludes: “Better understanding of immunity against melanocytes in melanoma, which clinically manifest as vitiligo, might contribute to the identification of other targets for immunotherapy against melanoma.”

Reference

Hua C, Boussemart L, Mateus C, et al. Association of Vitiligo With Tumor Response in Patients With Metastatic Melanoma Treated With Pembrolizumab.JAMA Dermatol 2015; Advance online publication 21 October. doi:10.1001/jamadermatol.2015.2707

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