Acta Dermato-Venereologica 99-1CompleteContent | Page 29
SHORT COMMUNICATION
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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