Acta Dermato-Venereologica 99-1CompleteContent | Page 29

SHORT COMMUNICATION 107 Unresectable Non-metastatic Primary Melanoma: Complete Remission Following Treatment with Anti-Programmed-cell-death-receptor 1 Coralie LHEURE 1,2 , Caroline HOFFMANN 3–5 , Nora KRAMKIMEL 1 , Julie PLEE 6 , Nathalie FRANCK 1 , Clélia VANHAECKE 6 , Gabrielle GOLDMAN-LÉVY 2,7 , Guillaume BATAILLON 8 , Diane DAMOTTE 2,7 , Nicolas DUPIN 1,2,9 , Selim ARACTINGI 1,2,10 , Florent GRANGE 6,11,12 and Sarah GUÉGAN 1,2,10 * Department of Dermatology and 7 Pathology, Assistance Publique–Hôpitaux de Paris (APHP), Cochin Hospital, 2 Paris Descartes University, Department of Head and Neck Surgery, 4 Unité INSERM U932 and 8 Department of Pathology, Institut Curie, 5 PSL University, Paris, 6 Department of Dermatology, CHU Reims, Robert Debré Hospital, Reims, 9 Institut Cochin, Inserm U1016, 10 Inserm UMRS938, Paris, 11 EA 7319, and 12 Reims Champagne-Ardennes University, Reims, France. *E-mail: [email protected] 1 3 Accepted Aug 31, 2018; Epub ahead of print Sep 3, 2018 Melanoma treatment has improved considerably fol- lowing the approval of immune checkpoint inhibitors and targeted therapy against BRAF and MEK (1, 2). In the melanoma tumour microenvironment, activated T cells can be functionally inactivated by engagement of the programmed-cell-death-receptor 1 (PD-1) with its ligands PD-L1 and PD-L2 expressed on tumour cells (3). Two monoclonal antibodies directed against PD-1 (nivolumab and pembrolizumab) have shown clinical efficacy in advanced melanoma (2, 4–7). Phase 3 trials have also demonstrated nivolumab and pembrolizumab superiority as adjuvant treatment in fully resected stage IIIB/C-IV melanoma (8, 9). But all trials centered on me- tastatic or locally advanced melanoma, and the efficacy of anti-PD-1 in non-metastatic primary melanoma has not been evaluated. We report herein 3 cases of patients with unresectable primary melanoma who achieved complete response after anti-PD-1 treatment. CASE REPORTS Case 1. A 60-year-old man was diagnosed with an unresectable primary mucosal melanoma of the oral cavity invading mouth, soft palate, uvula, cavum (Fig. 1a). The tumour did not display any BRAF, NRAS, or CKIT mutation. PD-L1 expression was negative on tumour cells and intermediate on immune cells (Fig. S1a-c 1 ). Anti-PD-1 therapy was quickly initiated. After 4 pemb- rolizumab infusions, partial clinical response was noted with the pigmented area extending only to the soft palate and uvula. A punch biopsy of this persisting lesion (Fig. 1b) performed after 10 infusions of anti-PD-1 revealed an infiltrate of melanophages surrounded by lymphocytes with no tumour cells (Fig. S1d 1 ). The patient tolerated the medication well, but presented with asymptomatic hyperthyroidism (anti-thyroid antibodies were all negative). Pembrolizumab was discontinued 6 months after this histologically confirmed remission, and no relapse occurred (12 months of follow-up). Case 2. An 89-year-old man was referred for a painful expanding lesion of the hard and soft palates (Fig. 1c), corresponding to a CKIT mutated mucosal melanoma (Fig. S1e 1 ), without metastatic disease on staging computing tomography (CT) scan and PET- scan. PD-L1 was highly expressed on tumour and immune cells (Fig S1f-g 1 ). Because of the limited efficacy of imatinib in CKIT mutated melanoma (10), anti-PD-1 therapy was initiated. After https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3028 1 Fig. 1. Clinical features of melanoma before and after anti- programmed-cell-death-receptor 1 treatment. Patient 1: mucosal melanoma (a) before and (b) after 10 infusions of pembrolizumab. White arrow indicates a residual pigmented macule. Patient 2: mucosal melanoma (c) before and (d) after 12 infusions of pembrolizumab. Patient 3: superficial spreading melanoma (e) before and (f) after 3 infusions of nivolumab. the third pembrolizumab course, the patient developed grade 2 polymyalgia rheumatica which quickly subsided with 0.5 mg/kg of oral corticotherapy. A significant reduction in tumour size was noted after the fourth pembrolizumab infusion. After the twelfth pembrolizumab infusion, 2 biopsies were performed on 2 residual lesions (Fig. 1d), and pathological analysis revealed a feature of complete regression with only melanophages and no tumour cells (Fig. S1h 1 ). Pembrolizumab was stopped after 13 anti-PD1 administrations. No relapse occurred (18 months of follow-up). Case 3. An 85-year-old woman was diagnosed with an NRAS mutated superficial spreading melanoma (SSM) of the foot (Fig. 1e), with 3 peripheral pigmented cutaneous metastases on the foot dorsum and no distant metastasis. Wide amputation was refused by the patient. No PD-L1 marker was expressed on tumour cells or on immune cells (Fig. S1j, k 1 ). Nivolumab was initiated: the goal was to obtain a sufficient response to allow surgical resec- tion without amputation. After 3 nivolumab infusions, the patient presented with rhabdomyolysis secondary to autoimmune related This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3028 Acta Derm Venereol 2019; 99: 107–108