P19: Systemic and Locoregional Efficacy of Talimogene laherparapvec in Advanced Melanoma

Introduction: Talimogene laherparapvec (Tvec) is an oncolytic viral therapy for advanced, unresectable melanoma. We examined use of Tvec in the setting of progression of disease (POD) on immunotherapy (IO) to characterize response to sequential therapy and Tvec in combination with immune checkpoint inhibitors.


Methods: A single institution retrospective cohort study of patients diagnosed with malignant melanoma, >18 years old, treated with Tvec between 2016-2022 with at least 6 month follow up post treatment including mortalities. Medical records were reviewed to collect demographic information, clinical characteristics, immunotherapy prior to Tvec treatment, and post-treatment outcomes (including local and systemic response to Tvec, and adverse effects). Descriptive statistics were performed to summarize the characteristics of the study population. χ² used to for comparative analysis of treatment subgroups.


Results: Of 133 patients who received Tvec during the study period, 82 met inclusion criteria. Median age at initiation of Tvec was 71 (range 30-95), 48 (58.5%) were male. Most patients (48.8%) were AJCC stage IV at time of first Tvec administration. Anatomically, most patients had cutaneous disease (n=58, 70.7%), while 10 (12.2%) patients had acral and 4 (4.9%) had mucosal with 12.5% other or unknown primary. Histologically, 12 (14.6%) patients had nodular type, 11 (13.4%) superficial spreading, 10 (12.2%) acral lentiginous, 3 (2.4%) desmoplastic, with 57.4% other or unclassifiable.
Most patients received immunotherapy before Tvec administration (n=63, 76.8%. 39(47.6%) patients received Tvec+IO combo therapy, 33(40.2%) received sequential therapy, and 10(12.2%) received Tvec alone. Over median follow up time of 28 months, overall locoregional response at final Tvec injection was 32.9% complete (CR), 34.1% partial (PR) and 9.76% stable disease (SD). There was no significant difference in locoregional response among the three treatment subgroups (p=0.26). In patients who started Tvec with stage IV disease, over a median follow up time of 12.5 months, systemic response at final Tvec injection was 10% CR, 5% PR, and 15% SD.


Conclusions: This study demonstrates the utility of Tvec for both locoregional and systemic disease sequentially and in combination with immune checkpoint blockade in patients who have experienced POD on prior IO. Locoregional response rates to Tvec were promising with almost a third achieving CR and another third showing PR. In stage IV patients, the systemic response rates were lower, yet there was still evidence of disease control in a proportion of patients.