Michael J Carr1, James Sun1,2, Danielle DePalo1, Luke D Rothermel1,3, Yun Song2, Richard J Straker4, Kristin Baecher5, Raphael J Louie6, Emma H A Stahlie7, G Paul Wright8, Syeda Mahrukh Hussnain Naqvi9, Youngchul Kim9, Amod A Sarnaik1, Giorgos C Karakousis4, Michael C Lowe5, Keith A Delman5, Alexander C J van Akkooi7, David W Ollila6, Frances Collichio10, Jonathan S Zager11,12. 1. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. 2. Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. 3. Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. 4. Department of Endocrine and Oncologic Surgery, University of Pennsylvania, Philadelphia, PA, USA. 5. Department of Surgical Oncology, Emory University, Atlanta, GA, USA. 6. Division of Surgical Oncology and Endocrine Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 7. Department of Surgical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands. 8. Department of Surgical Oncology, Spectrum Health/Michigan State University College of Human Medicine, Grand Rapids, MI, USA. 9. Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA. 10. Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 11. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. jonathan.zager@moffitt.org. 12. Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA. jonathan.zager@moffitt.org.
Abstract
BACKGROUND: Talimogene laherparepvec (T-VEC) is an oncolytic virus approved for the treatment of unresectable, recurrent melanoma. The role of T-VEC after progression on systemic immunotherapy (IO) remains undefined. The goal of this study was to characterize the efficacy of T-VEC after failure of IO in patients with unresectable metastatic melanoma. METHODS: An international, multi-institutional review of AJCC version 8 stage IIIB-IV melanoma patients treated with T-VEC after failure of IO was performed at six centers from October 2015-December 2020. Primary outcome was in-field response; secondary outcomes included analyses of in-field and overall progression-free survival (PFS) and in-field and overall disease-free survival (DFS) after a complete response. Subset analysis of T-VEC initiation sequentially after or concurrently with IO was performed. RESULTS: Of 112 patients, median age at T-VEC initiation was 69 years (range 21-93); 65 (58%) were male. Before T-VEC, 57% patients received one IO regimen, 42% received two or more, with most patients (n = 74, 66%) receiving T-VEC sequential to IO. Most were stage 3C (n = 51, 46%) at T-VEC initiation, 29 (26%) received injections to nodal disease. Over median follow-up of 14 months, in-field response at final T-VEC injection was 37% complete (CR), 14% partial (PR). T-VEC initiation sequentially or concurrently did not significantly affect in-field response (p = 0.26). Median in-field PFS was 15 months (95% confidence interval 4.6-NE). Median overall DFS after CR was 32 months (95% confidence interval 17-NE). CONCLUSIONS: T-VEC after failure of IO is effective in unresectable, metastatic stage IIIB-IV melanoma. T-VEC initiation sequentially or concurrently did not significantly affect in-field response.
BACKGROUND: Talimogene laherparepvec (T-VEC) is an oncolytic virus approved for the treatment of unresectable, recurrent melanoma. The role of T-VEC after progression on systemic immunotherapy (IO) remains undefined. The goal of this study was to characterize the efficacy of T-VEC after failure of IO in patients with unresectable metastatic melanoma. METHODS: An international, multi-institutional review of AJCC version 8 stage IIIB-IV melanoma patients treated with T-VEC after failure of IO was performed at six centers from October 2015-December 2020. Primary outcome was in-field response; secondary outcomes included analyses of in-field and overall progression-free survival (PFS) and in-field and overall disease-free survival (DFS) after a complete response. Subset analysis of T-VEC initiation sequentially after or concurrently with IO was performed. RESULTS: Of 112 patients, median age at T-VEC initiation was 69 years (range 21-93); 65 (58%) were male. Before T-VEC, 57% patients received one IO regimen, 42% received two or more, with most patients (n = 74, 66%) receiving T-VEC sequential to IO. Most were stage 3C (n = 51, 46%) at T-VEC initiation, 29 (26%) received injections to nodal disease. Over median follow-up of 14 months, in-field response at final T-VEC injection was 37% complete (CR), 14% partial (PR). T-VEC initiation sequentially or concurrently did not significantly affect in-field response (p = 0.26). Median in-field PFS was 15 months (95% confidence interval 4.6-NE). Median overall DFS after CR was 32 months (95% confidence interval 17-NE). CONCLUSIONS: T-VEC after failure of IO is effective in unresectable, metastatic stage IIIB-IV melanoma. T-VEC initiation sequentially or concurrently did not significantly affect in-field response.