Clinical and Histological Response to Talimogene Laherparepvec Therapy in Advanced Melanoma: Impact on Overall Survival

Background: Talimogene laherparepvec (T-VEC) is an FDA-approved oncolytic herpesvirus therapy used for unresectable stage IIIB through IV metastatic melanoma. However, the correlation between clinical complete response (cCR) and pathologic complete response (pCR) in patients treated with T-VEC is understudied.

Study design: We conducted a retrospective study from a prospectively maintained IRB-approved melanoma single-center database in patients treated with T-VEC from October 2015 to April 2022. Patients were categorized into 3 groups: cCR with pCR, cCR without pCR, and less than cCR. The primary endpoint was overall survival. We used descriptive statistics, chi-square tests, and Wilcoxon rank-sum tests to compare key covariates among exposure groups. We used survival analysis to compare survival curves and reported hazard ratio of death (95% CI) across exposure groups.

Results: We included 116 patients with a median overall survival (interquartile range) of 22.7 (14.8-39.3) months. The majority were men (69%) and White (97.4%), with a median age of 74.5 years. More than half of patients (n = 60, 51.6%) achieved cCR. Distribution among the groups was as follows: cCR with pCR (35.3%), cCR without pCR (16.3%), and less than cCR (48.4%). Median overall survival time (interquartile range) was 26.5 (18.6-36.0) months for cCR with pCR, 22.7 (14.4-35.5) months for cCR without pCR, and 17.8 (9.2-47.0) months for less than cCR (log-rank p value = 0.0033).

Conclusions: Patients achieving cCR with pCR after T-VEC therapy have the most favorable overall survival outcomes, whereas those achieving cCR without pCR have inferior survival and those achieving less than cCR have the poorest overall survival outcomes. These findings emphasize the importance of histological confirmation and provide insights for optimizing T-VEC therapy in patients with advanced melanoma.