BackgroundTalimogene laherparepvec (T-VEC) is a licensed therapy for use in melanoma patients of stage IIIB-IVM1a with injectable, unresectable metastatic lesions in Europe. Approval was based on the Oncovex Pivotal Trial in Melanoma study, which also included patients with distant metastases and demonstrated an overall response rate (ORR) of 40.5% and a complete response (CR) rate of 16.6%.ObjectivesThe aim of this study was to assess the outcome of melanoma patients treated with T-VEC in a real-life clinical setting.MethodsBased on data from 10 melanoma centers in Austria, Switzerland and southern Germany, we conducted a retrospective chart review, which included 88 patients (44 male, 44 female) with a median age of 72 years (range 36–95 years) treated with T-VEC during the period from May 2016 to January 2020.Results88 patients fulfilled the inclusion criteria for analysis. The ORR was 63.7%. 38 patients (43.2%) showed a CR, 18 (20.5%) had a partial response, 8 (9.1%) had stable disease and 24 (27.3%) patients had a progressive disease. The median treatment period was 19 weeks (range: 1–65), an average of 11 doses (range: 1–36) were applied. 39 (45.3%) patients developed adverse events, mostly mild, grade I (64.1%).ConclusionThis real-life cohort treatment with T-VEC showed a high ORR and a large number of durable CRs.

SummaryTalimogene laherparepvec (T‐VEC) is a intralesional oncolytic virotherapy, licensed in the European Union for locoregional advanced melanoma of American Joint Committee on Cancer stages IIIB, IIIC and IVM1a. Organ transplant recipients are currently excluded from all clinical trials dealing with immunotherapies due to the risk of transplant rejection. A 58‐year‐old white man with a history of heart and kidney transplantation in 2014 was diagnosed with melanoma (Breslow thickness 1·6 mm, stage pT2a) on the left arm in September 2015. In March 2016 he developed in transit metastases, and local therapy with a combination of topical imiquimod (5%) and cryotherapy of individual lesions was initiated. However, in November 2016 therapy was stopped following local progression of the metastases. An interdisciplinary decision to treat the patient with T‐VEC was taken. After 11 cycles of T‐VEC, the patient showed a complete response. As of June 2018, 11 months after the last treatment cycle of T‐VEC, the patient continues to be tumour free. The patient tolerated the therapy well with only mild adverse events and did not show any sign of graft rejection or loss of function of the transplanted organs. We conclude that T‐VEC can be a potentially effective and safe treatment in patients with a history of organ transplantation. Nevertheless, due to this special situation, the risks and benefits should always be discussed with an interdisciplinary tumour board.

Introduction:The implications of infiltrative compared to non-infiltrative growth of cutaneous basal cell carcinoma (BCC) on the tumor stroma and immune cell landscape are unknown. This is of clinical importance, because infiltrative BCCs, in contrast to other BCC subtypes, are more likely to relapse after surgery and radiotherapy. Materials and Methods: This descriptive cross-sectional study analyzed 38 BCCs collected from 2018 to 2021. In the first cohort (n = 28), immune cells were characterized by immunohistochemistry and multiplex immunofluorescence staining for CD3, CD8, CD68, Foxp3, and α-SMA protein expression. In the second cohort (n = 10) with matched characteristics (age, sex, location, and BCC subtype), inflammatory parameters, including TGF-β1, TGF-β2, ACTA2, IL-10, IL-12A, and Foxp3, were quantified via RT-qPCR after isolating mRNA from BCC tissue samples and perilesional skin. Results: Infiltrative BCCs showed significantly increased levels of α-SMA expression in fibroblasts (p = 0.0001) and higher levels of Foxp3+ (p = 0.0023) and CD3+ (p = 0.0443) T-cells compared to non-infiltrative BCCs. CD3+ (p = 0.0171) and regulatory T-cells (p = 0.0026) were significantly increased in α-SMA-positive tumor stroma, whereas CD8+ T-cells (p = 0.1329) and CD68+ myeloid cells (p = 0.2337) were not affected. TGF-β1 and TGF-β2 correlated significantly with ACTA2/α-SMA mRNA expression (p = 0.020, p = 0.005). Conclusion: Infiltrative growth of BCCs shows a myofibroblastic stroma differentiation and is accompanied by an immunosuppressive tumor microenvironment.

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9561 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic melanoma with objective response rates of 40-58%. However, reliable biomarkers to predict treatment response are lacking. Tumor tissue methylation profiles were recently proposed to have predictive value in various solid organ tumor entities. Methods: Patients with metastatic melanoma, American Joint Committee on Cancer (AJCC; 8th Edition) stage IV, receiving first-line ICI-based therapy, were retrospectively identified and formalin-fixed paraffin-embedded tumor tissue samples (FFPE) prior to ICI therapy were retrieved. We analyzed DNA methylation profiles of > 850.000 CpG sites in tumor specimens by Infinium MethylationEPIC microarrays. DNA methylation profiles were then correlated with radiological response (iRECIST). Results: 71 patients with metastatic melanoma (44 (62.0%) male, 27 (38.0%) female) were investigated; median progression free survival (PFS) was 8.5 months (range: 0 – 104.1 months) and median overall survival (OS) was 30.6 months (range: 0 – 104.1 months), respectively. 29 (40.8%) patients achieved an objective response to ICIs. Microarray analyses revealed a methylation signature including mainly hypomethylation, corresponding to the response to ICIs. Based on the 500 mostly differentially methylated genes, a total of 3 clusters were identified with the majority of responders being in cluster 2 (12/12) and 3 (12/22). The predictive performance of the methylation signature was high with 80% sensitivity, 81% specificity, and an AUC of 0.853. Conclusions: Our findings suggest that tumor DNA methylation profiling may be useful to predict response to ICIs in patients with metastatic melanoma.