Clinical and histopathological features of advanced cutaneous squamous cell carcinoma with varying responses to cemiplimab.

Background: Most patients with unresectable locally advanced cutaneous squamous cell carcinoma (cSCC) benefit from cemiplimab, but some do not respond. Our study aims to identify clinical and histopathological features predicting response to cemiplimab.

Patients and methods: We analyzed 15 patients treated with cemiplimab, assessing clinical, demographic, histopathological, and immunohistochemical characteristics and correlating them with treatment response. Furthermore, effectiveness and safety were evaluated in our cohort.

Results: Our cohort included 12 males and 3 females, with a mean age of 78.1 years. The majority of tumors, accounting for 66.7%, were located in the head and neck region. Treatment was well-tolerated, with only one grade 3 colitis. There was no correlation between immune-related adverse events and treatment response. Non-responders were younger (69.4 vs. 82.5 years). A history of hematological malignancy correlated with poorer response. High mitotic rate, poor tumor differentiation, high vimentin and p53, and low E-cadherin expression were associated with worse response. Conversely, higher intratumoral inflammatory infiltrate density, presence of necrotic areas, and lower mismatch repair-protein staining correlated with better response.

Conclusions: Cemiplimab is a safe and effective therapy, particularly in elderly patients. Well-differentiated tumors with low proliferative index, intratumoral inflammatory infiltrate, and tumor necrosis may predict better clinical response.