Regression of mucosal melanoma following intralesional talimogene laherparepvec (T‐VEC) injection in combination with immunotherapy

Abstract

We report on a 48-year-old female patient who had had a mucosal melanoma (tumor thickness: 7 mm, diameter: approximately 2.5 cm) removed from her left maxillary sinus in January 2016. As the lesion had been resected with only narrow tumor-free margins, she underwent adjuvant locoregional proton radiation therapy (total dose: 74 Gy) in March 2016. Computed tomography (CT) of the neck, abdomen and pelvis in June 2016 showed four new pulmonary lesions. In addition, cranial magnetic resonance imaging (MRI) showed a solitary metastasis of the left insular cortex measuring 1 cm in diameter, which was subsequently treated with stereotactic radiation therapy (total dose: 30 Gy). Combined immunotherapy consisting of four cycles of ipilimumab 3 mg/kg plus nivolumab 1 mg/kg every three weeks was initiated in September 2016, followed by nivolumab monotherapy (3 mg/kg) at two-week intervals. Both drugs activate the immune system, with ipilimumab inhibiting the cytotoxic T lymphocyte-associated antigen 4 (CTLA4), and nivolumab inhibiting the programmed cell death protein 1 (PD-1). Follow-up CT imaging at three and six months post treatment initiation showed only residual brain metastasis and stable pulmonary lesions. In February 2017, the patient experienced melanoma recurrence in the maxillary sinus, clinically characterized by nasal secretion, a fetid odor and signifi cant pain. Surgical reduction of the tumor burden in March 2017 brought only temporary relief. There was marked disease progression within just a few weeks, with tumor spread involving the maxillary sinus, the maxilla, the soft tissue of the cheek as well as the fl oor of the orbit and the pterygoid region (Figure 1 ). Molecular analysis subsequently revealed the tumor to be wild type for BRAF, NRAS and cKit. Given that another round of radiation therapy of this anatomic region was not possible and given that complete surgical resection would have resulted in signifi cant mutilation, we decided to start the patient on intralesional treatment with talimogene laherparepvec (T-VEC), an oncolytic herpes virus, beginning in July 2017. The fi rst of a total of three injections – given at three-week intervals – consisted of 2 ml of T-VEC at a concentration of 10 6 PFU/mL; the subsequent two injections, of 2 ml of T-VEC at a concentration of 10 8 PFU/mL. Immediately prior to injection, the patient received midazolam 7.5 mg intravenously (IV) and metamizole (dipyrone) 500 mg IV. The T-VEC injections were given under endoscopic control (nasal access) by a colleague from the Ear, Nose, and Throat Department (ENT) (Figure 2 ). After the procedure, the patient was monitored at the hospital for six hours. 24 hours after each injection, she developed swelling of the left side of the face as well as a erythema (Figure 3 ). She also reported fl u-like symptoms such as headache and myalgia as well as fever up to 39°C. Here, acetaminophen 500 mg taken orally once or twice daily over a period of seven days resulted in adequate symptom relief. While follow-up CT and endoscopy four weeks after the last injection showed signifi cant shrinkage of the recurrent tumor in the left maxillary sinus (Figure 1 ), there was no change in the size of the pulmonary lesions. Within just a few weeks after the fi rst T-VEC injection, the tumor-associated pain as well as the fetid odor and the nasal secretion showed considerable improvement.