Immunotherapy Significantly Improves Merkel Cell Carcinoma-Specific Survival: A Single-Cohort Propensity Score-Matched Analysis

BackgroundImmune checkpoint inhibitors (ICI) have improved outcomes in Merkel cell carcinoma (MCC). Population analyses suggest improved survival following the 2017 approval of ICI, but registry data lack treatment-level information including type of systemic therapy and initiation timepoint to directly estimate the benefit attributable to immunotherapy. This study compared Merkel Cell Carcinoma-specific survival between patients treated with first-line ICI versus cytotoxic chemotherapy. MethodsPatients were identified from the Seattle Merkel Cell Carcinoma Registry. Among 1,517 patients with MCC, 463 received first-line systemic therapy with either ICI or chemotherapy. Propensity scores were estimated using logistic regression including AJCC 8th stage, age, sex, MCPyV status, and immunosuppression. One-to-one nearest-neighbor matching produced balanced cohorts of 133 ICI-treated and 133 chemotherapy-treated patients. Merkel Cell Carcinoma-specific survival from therapy initiation was analyzed using Kaplan-Meier and Cox proportional hazards models with follow-up administratively censored at five years. ResultsBaseline clinical characteristics were comparable between matched cohorts. ICI therapy was associated with significantly improved Merkel Cell Carcinoma-specific survival compared with chemotherapy (log-rank p<0.0001). Five-year Merkel Cell Carcinoma-specific survival was 56.8% (95% CI 46.8-65.6) for ICI versus 23.9% (95% CI 16.9-31.6) for chemotherapy. In multivariable stage-stratified Cox analysis, ICI remained independently associated with improved Merkel Cell Carcinoma-specific survival (HR 0.32, 95% CI 0.21-0.50; p<0.0001), while immunosuppression was associated with worse Merkel Cell Carcinoma-specific survival (HR 2.03, 95% CI 1.10-3.74; p=0.0228). ConclusionsICI therapy was associated with substantially improved MCC-specific survival compared with chemotherapy.