Acta Dermato-Venereologica 99-2CompleteContent | Page 27

232 SHORT COMMUNICATION Induced Vitiligo due to Talimogene Laherparepvec Injection for Metastatic Melanoma Associated with Long-term Complete Response Pablo IGLESIAS 1# , Simone RIBERO 1,2# , Alicia BARREIRO 1 , Sebastian PODLIPNIK 1 , Cristina CARRERA 1 , Josep MALVEHY 1,3 and Susana PUIG 1,3 Dermatology Department, Hospital Clinic Barcelona, University of Barcelona, Villarroel 170, ES-08036 Barcelona, Spain, 2 Medical Sciences Department, Section of Dermatology, University of Turin, Turin, Italy and 3 Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Barcelona, Spain. E-mail: [email protected] # Both authors contributed equally to this paper. 1 Accepted Oct 3, 2018; E-published Oct 3, 2018 Talimogene laherparepvec (T-VEC) (Imlygic, Amgen) is the first oncolytic virus approved for use in therapy for metastatic melanoma. T-VEC provides a treatment op- tion for patients with limited metastatic disease. T-VEC is a genetically modified, live, attenuated herpes simplex virus type 1 designed to replicate in tumour cells and promote an enhanced anti-tumour response (1) T-VEC is administered by injection into cutaneous, subcutaneous or nodal lesions, which are visible and/or palpable and/ or visualized by ultrasonography (2). Other local management options have been used to control metastatic disease in stage IIIB, but almost all have shown only a local effect and rapid disease relapse (3, 4). With T-VEC, responses occurred in injected and unin- jected lesions, including a greater than 50% decrease in size in 15% of uninjected visceral lesions. The appearance of vitiligo has been described as an adverse event after administration of immune checkpoint inhibitors (5, 6). It has been reported as a marker of activity of the drug and long-term results, inducing clinicians to use it as a predictor of drug response (7). A T-VEC phase II study has reported 85% adverse events, all of which were grade 1 or 2. The appearance of vitiligo has been described in 3 patients out of 50 (8), although no details regarding duration and appearance have been reported. CASE REPORTS We describe here the appearance of a vitiligo phenomenon in the context of T-VEC therapy. Both patients were enrolled in a clinical trial after progression (Amgen 20120325, Eudra 2013-005552- 15). This trial consists of the injection of T-VEC in subcutaneous nodules of melanoma. We performed the injection under ultraso- nography. The patients had no active autoimmune disease or any history of such disease in the clinical records (those would be exclusion criteria for enrolment in the trial). Patient 1. The first patient was a 47-year-old man who had had a nodular ulcerated 3.2-mm melanoma, BRAF mutated, excised 3 years previously. The sentinel lymph node had a metastatic deposit of 2 mm maximum tumour diameter and the 9 lymph nodes excised at the complete lymph node dissection (CLND) were negative. Six months after surgery he noticed the appearance of a nodule close to the wide local excision scar (1 year after diagnosis of the primary tumour) followed by other 5 lesions on the same leg, which were confirmed to be cutaneous metastases. Radiological evaluation confirmed the absence of any other tumour deposit and he was enrolled in the trial 20120325, a total volume of 3.5 ml T-VEC at 108 PFU/ml was administered in 4 lesions. doi: 10.2340/00015555-3061 Acta Derm Venereol 2019; 99: 232–233 A total of 14 administrations every 3 weeks were needed to com- pletely shrink the metastases and to achieve a complete response. He developed a flu-like reaction after each administration. Two months after the last drug administration, hypochromic maculae appeared in some of the treated lesions on his leg (Fig 1). The patient remains in complete remission at 20 months. The size of the vitiligo has been stable since its first appearance (Fig. 1B) Patient 2. The second patient was a woman of 80 years, who had a BRAF wild-type melanoma, 1.87-mm Breslow thickness, excised from her right leg. Sentinel lymph node (SLN) biopsy was not carried out. Two and a half years after the first diagnosis she developed a lymph node metastasis in the groin and a meta- stasis on the skin graft of the wide excision. She was submitted to isolated limb perfusion with melphalan and tumour necrosis factor (TNF)-α) with a complete response. This was maintained for 14 months, when a new lesion (histologically confirmed) appeared on the same leg and she was treated with 26 cycles of T-VEC every 3 weeks, starting with an initial dose of 3 ml with a complete response. She developed a flu-like reaction after every administration. Two months after the last administration, some hypochromic areas appeared on her face, neckline and dorsum of her hands (Fig. 2). Seen under a Wood’s lamp, they were well de- limited and hypopigmented, suggestive of a vitiligo phenomenon. She remains in complete remission at 16 months. The vitiligo has been stable in size since its first appearance. DISCUSSION T-VEC was US Food and Drug Administration (FDA) approved for recurrent unresectable cutaneous and sub- cutaneous melanoma in October 2015. In a recent phase IIIB study, adverse events occurred in 93% of patients, with the most common being fatigue, chills, and pyrexia; grade ≥ 3 adverse events occurred in 24% of the T-VEC- treated group (9). Fig. 1. Case 1. (A) Well-defined hypochromic lesions with non-pigmented hairs on the pretibial area. Those lesions appeared at the sites of the previous melanoma metastases. (B) At 20 months from the complete response the vitiligo plaques were still visible and stable in size, as seen under Wood’s lamp. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.