Dynamic changes of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) during treatment with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC).

Abstract

2596 Background: ICIs have revolutionized the therapeutic landscape of NSCLC. However, with the exception of PD-L1 expression, predictive biomarkers are lacking. The aim of this study was to evaluate the dynamic changes of some markers of inflammation over time and the outcome of NSCLC patients (pts) treated with nivolumab (N) or pembrolizumab (P). Methods: All consecutive NSCLC pts treated with N or P between Aug. 2015-Dec. 2018 were analyzed. Laboratory results were collected at baseline, 6 weeks (6-wk), and 12 weeks (12-wk) and correlated with the outcome. NLR and PLR were defined as absolute neutrophil and platelet count divided by lymphocyte count, respectively. NLR ≥5, PLR ≥200, and LDH levels ≥ upper normal limit were considered high. Overall survival (OS) was defined as time from ICI start to death and Progression Free Survival (PFS) as time from treatment start to progression disease or death for any cause. OS and PFS curves were estimated using the Kaplan–Meier method and compared with the log-rank test. Results: We included 71 consecutive NSCLC pts treated with either N (75%) or P (25%). Baseline characteristics: median age 69 years (range 46-80), sex male 76%, squamous histology in 39%. PD-L1 expression (39/71): < 1% in 20%, 1-49% in 45%, and ≥50% in 35%. NLR ≥5 was associated with lower PFS and OS, with an increased predictive value over time ( p =0.01 and p =0.009 at baseline; p =0.007 and p <0.001 at 6-wk; p <0.001 and p <0.001 at 12-wk, respectively). PLR ≥200 at baseline and 12-wk was significantly associated with shorter OS ( p =0.05 and p =0.004, respectively), but no in terms of PFS at all the three time points. Finally, LDH ≥UNL at baseline was associated with shorter PFS and OS ( p =0.02 and p =0.03), as well as a reduction of LDH levels at 12-wk compared with baseline values ( p =0.006 and p =0.004). Conclusions: Baseline evaluation of NLR, PLR and LDH levels is significantly associated with outcome in NSCLC treated with single agent ICIs. Moreover, dynamic changes of LDH levels at 12 weeks significantly predicted outcome. These easy to determine parameters may have a place in the selection process of pts candidate for immunotherapy.