Acta Dermato-Venereologica 99-10CompleteContent | Page 22

913 SHORT COMMUNICATION Vitiligo Repigmentation with Melanoma Progression During Pembrolizumab Treatment Charlée NARDIN, Fabien PELLETIER, Eve PUZENAT and François AUBIN Department of Dermatology, University of Franche-Comte, EA-3181, Teaching Hospital, 3 Bd Fleming, FR-25030 Besancon cedex, France. E-mail: [email protected] Accepted Apr 16, 2019; E-published Apr 16, 2019 Vitiligo is an autoimmune skin disorder characterized by hypopigmented skin lesions, originating from the loss of functional melanocytes in the epidermis. Vitiligo can occur in patients suffering from melanoma and has long been recognized as an independent favourable prognostic factor for melanoma patients, correlating with impro- ved overall and tumour-free survival rates (1). Vitiligo has been reported in patients suffering from advanced melanoma, treated with immune checkpoint inhibitors (ICI) (2, 3). Furthermore, the onset of vitiligo in patients treated with the anti-PD-1 (programmed cell death 1 protein) antibody for advanced melanoma is associated with improved response and better outcomes (4–8). Here, we report a case of vitiligo re-pigmentation, which was associated with disease progression in a patient treated with pembrolizumab for metastatic melanoma. CASE REPORT A 50-year-old woman presented to our hospital with metastatic melanoma. She had a past medical history of left uveal melanoma, treated with surgery one year earlier. Molecular analysis of the metastatic liver lesion revealed a GNAQ mutation. She had no medical and family history of autoimmune diseases. A computed tomography (CT) scan showed liver, lung, brain, lymph nodes, subcutaneous, medullar and bone metastases with spinal cord compression. Pembrolizumab was initiated (2 mg/kg, every 3 weeks) simultaneously with radiation therapy for vertebral me- tastases. Paracetamol was prescribed for back pain. One month after pembrolizumab initiation, she developed extensive vitiligo (Fig. 1A). In addition, she developed hypothyroidism, without thyroid antibodies, and was treated with thyroid hormone therapy. At 3 months follow-up, CT scan showed stable disease (Fig. 1B). However, after 16 infusions of pembrolizumab (46 weeks of treatment), partial vitiligo re-pigmentation was observed on the face only. Of note, this occurred in the winter without any specific treatment or sun exposure (Fig. 1C). Lactate dehydrogenase (LDH) levels increased concomitantly (Fig. 2). CT scan was performed, and revealed disease progression (Fig. 1D). Fig. 1. Vitiligo re-pigmentation associated with melanoma progression during pembrolizumab treatment. (a) Extensive vitiligo in a patient treated with pembrolizumab for metastatic melanoma. (b) Axial CT section demonstrating stable disease with thoracic metastasis associated with extensive vitiligo. (c) Partial re-pigmentation of vitiligo after 16 infusions of pembrolizumab. (d) Axial CT section demonstrating disease progression with an increase in thoracic metastasis associated with vitiligo re-pigmentation. DISCUSSION Vitiligo is one of the most frequent dermatologic adverse events of the anti-PD-1 therapy in cancer immuno­ therapy (2). In a meta-analysis, the incidence of all-grade vitiligo was around 8% with immunotherapy (2). The incidence of vitiligo in melanoma patients, treated with pembrolizumab, has been reported to be up to 25% (4). As compared to patients under chemotherapy, vitiligo is reported to be more frequent in patients treated with nivolumab or pembrolizumab (2). In the literature, Fig. 2. Kinetics of serum biomarkers over time. Lactate dehydrogenase (LDH) rate only seemed to decrease with vitiligo and disease control while rising at the time of vitiligo re-pigmentation and disease progression. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3199 Acta Derm Venereol 2019; 99: 913–914