Intralesional talimogene laherparepvec for treatment of advanced merkel cell carcinoma

Summary: Abstract Body: Merkel cell carcinoma (MCC) is an aggressive skin cancer with rising incidence. While ~50% of patients with advanced MCC respond to immune checkpoint inhibitors (ICIs), those who discontinue ICIs due to side effects or lack of response require alternative treatment options. Talimogene laherparepvec (T-VEC), a modified oncolytic herpes simplex virus, is commonly used for advanced melanoma. However, data on its use in MCC are limited, primarily consisting of case reports with one or two responders, making it challenging to comprehensively evaluate responses and associated clinical features. Here, we report on eight metastatic MCC patients treated with TVEC at two institutions. All had disease progression following ICI or chemotherapy, and two were immunosuppressed due to hematologic malignancies. Five of the eight patients achieved an objective response (OR), with three partial (PR) and two complete responses (CR). The median time to OR was 8 months (range 1.2–14.4). All ORs except one were sustained for at least 10 months after best response. The abscopal effect was minimal. Three patients had non-injectable lesions that either progressed or remained stable in size, at best, throughout T-VEC therapy. Grade 2 and 3 side effects occurred in three patients. Pathological analysis of pre- and post-treatment biopsies were carried out in two patients. Prior to treatment, the responder had more viable tumor content and higher mitotic activity than the non-responder. In the post-treatment biopsies, the responder had more tumor necrosis with prominent lymphohistiocytic inflammation compared to the non-responder. In conclusion, TVEC demonstrates potential as a minimally toxic and salvage therapy that provided meaningful clinical benefit for 5 of 8 patients with therapeutically refractory MCC. Smitha Chandrasekhar¹, Emily T. Huynh^{1, 2}, Melissa M. Yamada³, Bicong Wu¹, Paul Nghiem^{1, 4}, David Chen³, Song Y. Park^{1, 4} 1. Dermatology, University of Washington, Seattle, WA, United States. 2. Pacific Northwest University of Health Sciences, Yakima, WA, United States. 3. Dermatology, Washington University in St Louis, St. Louis, MO, United States. 4. Fred Hutchinson Cancer Center, Seattle, WA, United States. Clinical Research: Epidemiology and Observational Research