Rate of complete and durable responses of intralesional therapy with talimogene laherparepvec for stage IIIB-IVM1a melanoma and association with tumor load.

Abstract

e22089 Background: Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex type 1 virus, which is used as an oncolytic immunotherapy in stage IIIB-IVM1a melanoma patients. It is known to be an effective therapy for injectable cutaneous, subcutaneous and nodal melanoma lesions, as approved by the European Medicines Agency (EMA). Combination therapy is not yet approved by EMA pending the results of the phase 3 Masterkey-265 trial. The objective of the current study was to identify prognostic factors for achieving a complete response (CR) that can be used to select patients for treatment with T-VEC monotherapy. Methods: Patients with stage IIIB-IVM1a melanoma, treated with T-VEC at the Netherlands Cancer Institute between 2016-12 and 2019-05 with a follow-up time > 6 months, were included. Data was collected on baseline characteristics, responses and adverse events (AEs). Durable response rate (DRR) was defined as the percent of patients with a CR or partial response (PR) maintained continuously > 6 months. Univariable analyses were conducted and a prediction model was developed to identify prognostic factors associated with complete response. Results: For this study, a total of 71 patients were included with a median follow-up of 16.1 months. The median age was 70 years (range: 35-90). As best response, 47 patients (66%) had a CR and 10 patients (14%) had a PR, resulting in an overall response rate of 80%. Twenty-one patients (30%) stopped treatment because of progressive disease and sixteen patients (23%) developed a recurrence during follow-up after achieving a PR or CR. Median duration of CR was 11 months. The durable response rate was 42%. Grade 1-2 AEs occurred in almost every patient. Tumor size, type of metastases, previous treatment with systemic therapy and stage (8Th AJCC) were independent prognostic factors for achieving a CR and for progression-free survival. Achieving a CR was associated with a reduced risk of death. The prediction model includes tumor size, type of metastases (only cutaneous vs. subcutaneous (+/- cutaneous) vs. nodal (+/- cutaneous/subcutaneous)) and number of lesions as predictors. Conclusions: This study shows that intralesional T-VEC monotherapy for stage IIIB-IVM1a melanoma is able to achieve high complete and durable response rates. The prediction model shows that use of T-VEC in patients with less tumor burden is associated with better outcomes, suggesting T-VEC should perhaps be used earlier in the course of the disease.