Background: Prognostic factors for initial response of advanced cutaneous squamous cell carcinoma to cemiplimab treatment are lacking. Il-6 has been found to affect immune cell populations which impact tumor development. The aim was to investigate the prognostic significance of IL-6 serum levels before and during treatment. Methods: Serum levels of IL-6 were correlated with clinical outcomes in a retrospective study. Results: Overall, 39 patients were enrolled. High serum levels of IL-6 (> 5.6 pg/ml) were associated with poorer survival (45.1% vs 0 deaths; OS: 16.1 ± 1.5 vs 20.8 ± 0 months, 95% CI 13,046 to 19,184) and shorter PFS (10.3 ± 1.9 vs 18.9 ± 1.5 months; 95% CI 3433 to 10,133) in patients with advanced CSCC treated with cemiplimab. In addition, patients whose IL-6 level increased after treatment with cemiplimab, independently of the basal level, had a poorer response to treatment than patients whose level was reduced or stable after immunotherapy. Conclusions: Serum levels of IL-6 at baseline and changes after cemiplimab immunotherapy may have a prognostic significance in patients with advanced cutaneous squamous cell carcinoma.

Purpose of Review: The treatment strategy for BRAF-mutated melanoma remains unsatisfactory, although the advent of immune checkpoint inhibition has improved the prognosis of advanced melanoma. This article reports current evidence on the efficacy and safety of sequential immunotherapy with targeted therapy in patients with BRAF-mutated melanoma. It discusses criteria for the use of available options in clinical practice. Recent Findings: Targeted therapy provides rapid disease control in a relatively high proportion of patients, although the development of secondary resistance limits the duration of responses; in contrast, immunotherapy may induce slow but more durable responses in a subset of patients. Summary: Therefore, the identification of a combination strategy for the use of these therapies seems a promising perspective. Currently, inconsistent data have been obtained, but most studies indicate that the administration of BRAFi/MEKi prior to immune checkpoint inhibitors appears to reduce the efficacy of immunotherapy. On the contrary, several clinical and real-life studies suggest that frontline immunotherapy with subsequent targeted therapy may be associated with better tumor control than immunotherapy alone. Larger clinical studies are ongoing to confirm the efficacy and safety of this sequencing strategy for treating BRAF-mutated melanoma with immunotherapy followed by targeted therapy.

Patients with pre-existing autoimmune disease (AID) are underrepresented in trials of immune checkpoint inhibitors (ICIs). We retrospectively compared 41 patients with stage IV melanoma and pre-existing AID with 162 contemporaneous controls without AID who received ICI treatment between November 2016 and April 2023. In the AID and control cohorts, respectively, the objective response rates were 46.3% and 32.7%, and the disease control rates were 80.5% and 51.2%. Treatment interruption attributed to worsening of the baseline AID was recorded in 11/41 patients, while 13/41 interrupted treatment because of toxicity distinct from the baseline AID. The full cohort contributed 114 progression-free survival (PFS) events and 92 deaths. In models adjusted for age, sex, ICI regimen and M category, AID was associated with PFS (adjusted hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.24–0.99; p = 0.046), whereas the association with overall survival (OS) was not statistically significant (adjusted HR 0.63, 95% CI 0.29–1.34; p = 0.232). These findings support the feasibility of ICI therapy in carefully selected patients with clinically stable AID, while the observational design and residual confounding require cautious interpretation of comparative outcomes.