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.

BackgroundImmune checkpoint inhibitors (ICPis) have revolutionised the treatment of melanoma by significantly increasing survival rates and disease control. However, ICPis can have specific immune-related adverse events, including rare but severe neurological toxicity.Case presentationWe report a 44-year-old man diagnosed with stage IIIB melanoma who developed metastatic disease (pulmonary and brain metastases) and was treated with stereotactic radiosurgery and nivolumab immunotherapy. He developed asymptomatic multifocal diffuse white matter lesions consistent with active central nervous system demyelination seen on brain MRI. One month after cessation of the immunotherapy, spontaneous regression of the demyelinating lesions was observed, suggesting a nivolumab-related toxicity.ConclusionWe report the first case of a melanoma patient with an asymptomatic and spontaneously reversible central nervous system demyelination following nivolumab immunotherapy. This case highlights the need for better recognition of such atypical and rare neurological toxicities which could be mistaken for progressive brain metastases. Early recognition and appropriate management are crucial to reduce severity and duration of these toxicities, especially for patients with less favourable evolution.

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We report a case of an uveal melanoma patient with GNAQ p.Gly48Leu who responded to MEK inhibition. At the time of the molecular analysis, the pathogenicity of the mutation was unknown. A tridimensional structural analysis showed that Gαq can adopt active and inactive conformations that lead to substantial changes, involving three important switch regions. Our molecular modelling study predicted that GNAQ p.Gly48Leu introduces new favorable interactions in its active conformation, whereas little or no impact is expected in its inactive form. This strongly suggests that GNAQ p.Gly48Leu is a possible tumor-activating driver mutation, consequently triggering the MEK pathway. In addition, we also found an FGFR4 p.Cys172Gly mutation, which was predicted by molecular modelling analysis to lead to a gain of function by impacting the Ig-like domain 2 folding, which is involved in FGF binding and increases the stability of the homodimer. Based on these analyses, the patient received the MEK inhibitor trametinib with a lasting clinical benefit. This work highlights the importance of molecular modelling for personalized oncology.

Background: Immune-related adverse events (IrAEs) associated with the use of immune checkpoint inhibitors (ICIs) may not be fully covered by existing measures like the PRO-CTCAEä. Selecting PRO-CTCAEä items for monitoring symptomatic adverse events is hindered by the heterogeneity and complexity of IrAEs, and no standardised selection process exists.