Neoadjuvant Talimogene Laherparepvec for the Treatment of Metastatic Melanoma

Wide local excision of the left ear melanoma was performed with a 2-cm margin of resection along with sentinel lymph node biopsy of two level II cervical nodes. Postoperatively, positron emission tomography-computed tomography (PET-CT) was notable for new hypermetabolic lymphadenopathy in the posterior cervical triangle as well as an FDG avid nodular soft tissue density anterior to the parotid gland; both of which were felt to represent recurrent disease. After lengthy discussions with the patient along with multidisciplinary conference consultation, the patient was screened and enrolled into the neoadjuvant T-VEC trial (NCT02211131) comparing neoadjuvant intralesional T-VEC followed by surgery to surgery alone for patients with stage IIIB-IVM1a metastatic melanoma. The virus has been altered by functionally deleting the nonessential ICP34.5 and ICP47 virulence genes thus limiting the virus's effect on human cells and increasing its ability for replication and tumor cell lysis.2 When combined with the insertion and encoding of the GM-CSF gene, this leads to both an immunogenic and viral oncolytic effect on melanoma cells (Fig. 2). In 2006, results were published from a Phase I study of an oncolytic HSV-1-expressing GM-CSF (OncoVEXGM-CSF) administered via intratumoral injection in patients with refractory cutaneous/subcutaneous breast, head and neck, gastrointestinal, or melanoma metastases.3 Of the nine patients with melanoma included in the study, five had flattening or shrinkage of the injected lesion with treatment and four had evidence of tumor necrosis on biopsy. The treatment was generally well tolerated, even with multiple treatments, with the most common adverse reactions being local inflammatory...