Clinical, Pathologic, And Genomic Profiles Of Exceptional Responders To Anti-Pd1 Therapy In Renal Cell Carcinoma.

625 Background: Previous studies have correlated response to PD−1 blockade with PD−L1 over−expression, as well as cell−mediated immune transcripts). However, factors associated with long−term, durable response to nivolumab in patients with RCC have not yet been elucidated. To better understand these factors, we conducted a study to characterize the two extremes of response to therapy – exceptional responders who had durable, complete response and patients who had primary refractory disease. Methods: Patients with durable, complete response (“exceptional responders”) (n=4) and primary refractory disease (n=3) were analyzed. Immunohistochemical staining for PD−L1, CD8 and FOXP3, whole−exome sequencing and quantitative RNA expression profiling was performed and correlated with clinical outcomes. Results: Exceptional responders had trends toward greater CD8+ lymphocyte infiltrate (126.7 vs 28.8 lymphocytes/hpf), higher number of somatic mutations (67 vs 35 somatic mutations/genome), and higher number of predi...