Genetic Factors Associated with Clinical Response in Melanoma Patients Treated with Talimogene Laherparapvec: A Single-Institution Retrospective Analysis.

Background: Talimogene laherparapvec (T-VEC) is a modified herpes simplex virus type 1 (HSV-1) and the first oncolytic virus to be approved for the treatment of unresectable melanoma. We assessed whether there are tumor-intrinsic genetic factors that are associated with tumor control.

Methods: A single-institution, retrospective analysis of melanoma patients treated with T-VEC was performed. Demographics, histopathologic reports, treatment history, clinical outcomes, and tumor genomic analysis of approximately 100 genes were collected.

Results: Ninety-three patients who had received T-VEC were identified, of whom 84 (91%) were diagnosed with cutaneous melanoma. Sixty-nine (69) patients received more than one dose of T-VEC and had sufficient data available for clinical analysis. Of these patients 30.0% (n = 21) had evidence of a complete response, defined as complete regression of all lesions without the need for additional treatment or procedures. Stage III disease (p < 0.001), absence of macroscopic nodal disease (p < 0.001), and absence of visceral/central nervous system metastases (p = 0.004) were all associated with evidence of any clinical response or local control by univariate analysis. At the time of analysis, 54 patients had tumor genetic data available. Sixty genes were mutated in at least one patient, and all but one patient had at least one gene mutation identified. Presence of TERT promotor mutation was associated with evidence of any clinical response (p = 0.043) or local control (p = 0.039) by multivariate analysis.

Conclusions: This work describes the experience using T-VEC in melanoma at a single institution and highlights the presence of TERT promotor mutations as a possible driver of clinical response.