Change in Neutrophil-to-lymphocyte Ratio in Response to Targeted Therapy for Metastatic Renal Cell Carcinoma as a Prognosticator and Biomarker of Efficacy
Menée à partir de données portant sur 1 199 patients atteints d'un carcinome métastatique à cellules rénales et ayant reçu une thérapie ciblée (âge médian : 62 ans), puis validée sur 4 350 patients complémentaires inclus dans des essais cliniques (âge médian : 59 ans), cette étude évalue l'association entre l'évolution du rapport neutrophiles/lymphocytes (calculé avant puis 6 et 8 semaines après le traitement) et la survie globale, la survie sans progression ou le taux de réponse objective
Background : Neutrophil-to-lymphocyte ratio (NLR), if elevated, is associated with worse outcomes in several malignancies.
Objective : Investigation of NLR at baseline and during therapy for metastatic renal cell carcinoma.
Design, setting, and participants : Retrospective analysis of 1199 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC cohort) and 4350 patients from 12 prospective randomized trials (validation cohort).
Intervention : Targeted therapies for metastatic renal cell carcinoma.
Outcome measurements and statistical analysis : NLR was examined at baseline and 6 (± 2) wk later. A landmark analysis at 8 wk was conducted to explore the prognostic value of relative NLR change on overall survival (OS), progression-free survival (PFS), and objective response rate using Cox or logistic regression models, adjusted for variables in IMDC score and NLR values at baseline.
Results and limitations : Higher NLR at baseline was associated with shorter OS and PFS (Hazard Ratios [HR] per 1 unit increase in log-transformed NLR = 1.69 [95% confidence interval {CI} = 1.46–1.95] and 1.30 [95% CI = 1.15–1.48], respectively). Compared with no change (decrease < 25% to increase < 25%, reference), increase NLR at Week 6 by 25–50% and > 75% was associated with poor OS (HR = 1.55 [95% CI = 1.10–2.18] and 2.31 [95% CI = 1.64–3.25], respectively), poor PFS (HR = 1.46 [95% CI = 1.04–2.03], 1.76 [95% CI = 1.23–2.52], respectively), and reduced objective response rate (odds ratios = 0.77 [95% CI = 0.37–1.63] and 0.24 [95% CI = 0.08–0.72], respectively). By contrast, a decrease of 25–50% was associated with improved outcomes. Findings were confirmed in the validation cohort. The study is limited by its retrospective design.
Conclusions : Compared with no change, early decline of NLR is associated with favorable outcomes, whereas an increase is associated with worse outcomes.
Patient summary : We found that the proportion of immune cells in the blood is of prognostic value, namely that a decrease of the proportion of neutrophils-to-lymphocytes is associated with more favorable outcomes while an increase had the opposite effect
European Urology , résumé, 2015