Talimogene laherparepvec with systemic immunotherapy in melanoma: A real-world experience.

Abstract

e21549 Background: Talimogene laherparepvec (TVEC) is an FDA approved oncolytic herpes virus for intralesional therapy in unresectable metastatic melanoma. Real world data is sparse regarding the efficacy of TVEC in combination with other systemic therapies used in melanoma. We present outcomes of the largest single institution observational study of the off-label use of TVEC in combination with systemic immunotherapy. Methods: Patients with metastatic melanoma receiving TVEC simultaneously with ipilimumab-nivolumab (Ipi/Nivo) or single agent immunotherapy (either nivolumab or pembrolizumab) were evaluated. The demographics, clinicopathological characteristics, responses to injected lesions and remote metastatic lesions were evaluated. Clinical documentation was used to assess improvement in injected lesion size; time points for initial response and best response were identified. Review of imaging by a radiologist was evaluated to assess responses in remote metastatic lesions. Results: A total of 67 patients receiving TVEC from 2016 to 2020 were evaluated, of which 50 remained evaluable after excluding Merkel cell carcinoma, patients on clinical trial, TVEC monotherapy or those on BRAF-MEK inhibitors, and patients lost to follow up. In total, 29 received systemic immunotherapy simultaneously with TVEC and had been followed for at least a year, with a median follow-up time of 34 months (range, 12-56). At the time of analysis, 14 of 29 patients were alive. 6 of the 29 patients had received prior lines of therapy. Four patients received Ipi/Nivo, while 25 patients received monotherapy including 9 on nivolumab and 16 on pembrolizumab. The median number of TVEC doses received was 6 (range, 2-55) with median average TVEC dose being 3.47 ml (0.5-4 ml). Median time to initial local response was 6 weeks, whereas time to best local response was 14 weeks. Overall response rate in the injected target lesions was in 19 (66%), with complete local response (CR) in 12 (41%), partial response (PR) in 7 (24%), and progressive disease (PD) in 8 (28%). The response rate in distant non-injected lesions was 4 out of 16 (25%), 2 of which had previously progressed on prior systemic therapy. Stable disease was observed in 8 (50%) patients, and progression of disease in 4 (25%). The 1-year overall survival rate in patients receiving TVEC with systemic monotherapy was 80%, 95% CI 0.651-0.9730. Progression free survival at 1-year in the monotherapy group was 71.6%, 95% CI 0.557-0.918. Conclusions: This is the largest single institution, real world experience to our knowledge, which assesses the efficacy of TVEC in combination with systemic immunotherapy. Our cohort suggests that TVEC is an effective treatment in combination with systemic immunotherapy, with a better overall survival observed with combination TVEC and anti-PD1 than seen with historical data from clinical trials of anti-PD-1 monotherapy.