Change in neutrophil to lymphocyte ratio as a prognostic and predictive marker in response to targeted therapy for metastatic renal cell carcinoma.

Abstract

404 Background: The neutrophil to lymphocyte ratio (NLR) is a marker of inflammation. We evaluated whether NLR is independently prognostic when adjusted for the International mRCC Database Consortium (IMDC) model and evaluated change in NLR ("NLR conversion") as a predictive marker of response to targeted therapy. Methods: A total of 5,227 metastatic renal cell carcinoma (mRCC) patients treated with targeted therapy were included; 1,199 patients in the training cohort from the IMDC and 4028 patients as the validation cohort from pooled prospective randomized controlled trials involving targeted therapy. NLR was examined at initiation of first-line targeted therapy and at 6 weeks after. The prognostic role of NLR and NLR conversion on overall survival (OS) and progression free survival (PFS) was assessed using Cox regression models adjusting for IMDC prognostic score. Results: Median baseline NLR was 3.4 and 2.9 in the training and validation cohorts, respectively. NLR >3.0 at baseline was independently associated with OS and PFS in both the training and validation cohorts (Table). A decrease in NLR by week 6 was associated with longer OS (21.1 vs. 9.7 months; HR 0.57, p<0.001), PFS (8.8 vs. 4.6 months; HR 0.54, p<0.001), and higher objective response rates (35% vs. 13%, p<0.001) compared to patients without a decrease. A rise in NLR showed opposite effects for all three endpoints. These findings were also confirmed in the validation set. Conclusions: NLR is an independent prognostic factor after controlling for IMDC criteria. NLR conversion can be an early biomarker of benefit to targeted therapy. [Table: see text]