374P - Prognostic relevance of post-cycle 1 pembrolizumab levels in real-world NSCLC patients receiving first line IO or ChIO

Background

Antibodies against Programmed Cell Death Protein 1 receptor (PD-1) or its ligand (PD-L1) are standard of care for NSCLC. However, they are not effective for all patients, making predictive biomarkers necessary. Pembrolizumab, an IgG antibody against PD-1, is approved at 2 mg/kg or 200 mg every 3 weeks. Its plasma levels may vary due to clearance differences, potentially affecting PD-1 blockade and patient outcomes.

Methods

Pembrolizumab plasma levels after first cycle (C1), were evaluated in 133 patients receiving first-line pembrolizumab monotherapy (IO) or combined with chemotherapy (ChIO), through ELISA (Matriks Biotek). Free PD-1 receptor (i.e not-bound to pembrolizumab) in blood lymphocytes at C1 was determined in 82 cases by flow cytometry. C1 levels were categorized as High or Low (cut-off=10 μg/mL). Kaplan-Meier and log-rank test were used for survival analysis. Correlations of baseline dose, BMI, BSA, and albumin with pembrolizumab C1 levels were done in 57 patients with extended clinical data.

Results

Low pembrolizumab C1 levels were associated with worse survival (PFS HR 2.1, p=0.0003; OS HR 3.1, p < 0.0001) for all patients. IO alone (n=53) (PFS HR 1.8, p=0.087; OS HR 2.1, p=0.069) and ChIO (n=80) (PFS HR 2.4, p=0.0006; OS HR 3.8, p < 0.0001) showed similar results. Lower pembrolizumab C1 levels were associated with higher free PD-1 on CD4+ (r=−0.42, p < 0.0001) and CD8+ lymphocytes (r=−0.25, p=0.023); and to male sex (χ2 p=0.008). In the subcohort with extended clinical data, pembrolizumab C1 levels correlate with initial dose (r=0.33, p=0.01) and more strongly with albumin levels (r=0.54, p=0.008), supporting differences in drug clearance via the neonatal Fc receptor (FcRn).