Predictors of response and survival in cemiplimab–treated cutaneous squamous cell carcinoma: multicenter real-world evidence from Germany

Abstract Purpose To assess the association of systemic immune-inflammation biomarkers (SIIBs) and other clinical parameters with objective response rate (ORR), progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS), and immune-related adverse events (irAEs) in patients with advanced cSCC treated with cemiplimab, and to compare baseline SIIBs levels between early-stage and advanced-stage disease. Methods A retrospective multicenter cohort of 110 immunocompetent advanced cSCC patients treated with cemiplimab was analysed. ORR was assessed using logistic regression; PFS and OS were evaluated using Cox models, and DSS using cause-specific hazards. ROC analyses assessed biomarker discrimination. Baseline SIIBs (LMR, NLR, SIRI) were compared between early-stage (AJCC I/II, non-ICI cohort, n = 59) and advanced-stage disease. Tumor characteristics, body mass index (BMI), and Charlson comorbidity index were evaluated. Results Among 110 patients, 79 (71.8%) achieved an objective response. Baseline LMR showed modest discrimination for ORR (AUC 0.64, 95% CI 0.53–0.75; p = 0.015) but did not retain statistical significance after adjustment for baseline clinical covariates (OR 1.35, 95% CI 0.95–1.91; p = 0.096). Higher BMI was associated with improved PFS (HR 0.94 per kg/m 2 , 95% CI 0.89–1.00; p = 0.035) and showed a borderline association with OS (HR 0.92 per kg/m 2 , 95% CI 0.85–1.00; p = 0.051). AJCC stage IV strongly predicted DSS (HR 14.03, 95% CI 1.80–109.67; p = 0.012). Baseline LMR was higher in early-stage than in advanced-stage disease (Hodges-Lehmann difference 0.43; p = 0.011), whereas NLR did not differ significantly between stage groups; SIRI was modestly higher in advanced-stage disease ( p = 0.029). Conclusions In immunocompetent patients with advanced cSCC receiving PD-1 inhibition, BMI was prognostic for survival and AJCC stage remained the key driver of cSCC-specific mortality. Baseline LMR showed a modest association with response and differed between early- and advanced-stage disease, whereas other SIIBs were not consistently linked to tumor progression. Prospective validation is warranted.