CTLA-4 blockade with ipilimumab increases peripheral CD8+ T cells: Correlation with clinical outcomes.

2555 Background: Increasing doses of ipilimumab, an antibody to CTLA-4, is associated with a higher likelihood of clinical benefit. Analysis of pharmacodynamic biomarkers shows the magnitude of absolute lymphocyte count (ALC) increase correlates with dose. Identifying the lymphocyte subpopulations specifically increased may further elucidate the mechanism of action of CTLA-4 blockade. In a pooled analysis of four phase II trials (CA184-045, -008, -078, -042), peripheral blood lymphocytes subsets were analyzed from 35 patients (pts) with advanced melanoma treated with ipilimumab at Memorial Sloan-Kettering. Methods: Ipilimumab was administered (10 mg/kg every 3 weeks × 4 doses) and eligible pts continued to receive ipilimumab maintenance therapy every 12 weeks starting at week 24 in the setting of disease control. Under an institutional IRB- approved correlative blood drawing protocol, peripheral blood was obtained at weeks 1 (pre-treatment) and 7 (just before 3rd dose) and lymphocyte counts determined and...