Ioannis P. Trontzas, Anastasia Palaiologou, Natalia Kamperi, Anastasia Georganta, Emmanouil Panagiotou, Ioanna-Maria Orfanou, Konstantinos G. Kyriakoulis, Ioannis Vathiotis, Ηλίας Κοττέας, Dimitra Grapsa, Constantin Tamvakopoulos, Konstantinos N. Syrigos
BACKGROUND: Therapeutic drug monitoring (TDM) of immune checkpoint inhibitors (ICIs) remains limited due to drug-related challenges; however, a better understanding of exposure-effect relationships may improve antitumor activity and reduce immune-related adverse events (irAEs). METHODS: We conducted a prospective TDM study measuring pembrolizumab trough concentrations (Cmin) using a commercial ELISA kit in 31 patients with advanced non-small cell lung cancer (NSCLC) receiving pembrolizumab monotherapy. Serial Cmin measurements were obtained at baseline (T0), before cycle 2 (T1), and at 3 (T2), 6 (T3), and 12 months (T4). Baseline clinicopathologic and serologic variables were recorded. Patients were followed for 2 years to assess treatment outcomes. RESULTS: = 0.25). Higher Cmin levels at later timepoints were associated with improved clinical outcomes. Elevated Cmin correlated with a greater number of organ systems affected by irAEs. High baseline albumin and fewer comorbidities were predictors of higher Cmin. CONCLUSIONS: Pembrolizumab TDM is a feasible approach in NSCLC. Higher late-treatment Cmin levels may be associated with favorable outcomes, supporting pembrolizumab exposure as a potential biomarker and highlighting TDM as a tool for dose-tailoring strategies.