Clinical implications of neutrophil-to-lymphocyte ratio and MDSC kinetics in gastric cancer patients treated with ramucirumab plus paclitaxel

Objective: We aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and myeloid-derived suppressor cells (MDSCs) in gastric cancer patients treated with second-line ramucirumab plus paclitaxel. Methods: A total of 116 patients with advanced or metastatic gastric cancer who receive ramucirumab plus paclitaxel were prospectively enrolled. Fresh blood samples were collected before and after treatment, and flow cytometry was performed to assess the proportions of monocytic (mMDSCs) and granulocytic MDSCs (gMDSCs). Results: Median age was 58 years and 71 (61.2%) patients were male. A baseline NLR=2.94 was associated with significantly poorer progression-free survival (PFS) and overall survival (OS) vs. an NLR<2.94 (P=0.011 and P=0.002, respectively). In multivariate analysis, an NLR=2.94 was independently associated with poorer PFS [hazard ratio (HR)=1.58; 95% confidence interval (95% CI): 1.01-2.49, P=0.046] and OS (HR=1.77; 95% CI: 1.04-3.04, P=0.036). While mMDSC counts did not significantly change following two cycles of therapy (P=0.530), gMDSC counts decreased significantly after two treatment cycles (P=0.025) but tended to increase in patients with progressive disease after two treatment cycles (P=0.098). A progressive increase in gMDSC counts (<44%) was associated with a significantly shorter PFS and OS vs. a gMDSC count increase <44% (P=0.001 and P=0.003, respectively). Conclusions: The baseline NLR may help guide clinical decisions during ramucirumab plus paclitaxel therapy for gastric cancer. Our gMDSC kinetics data warrant further clinical validation and mechanistic investigation.