Abstract 2607: Blood based biomarkers and association with clinical outcome (CO) in advanced stage patients (pts) treated with immunotherapy (IO)
Authors: Martini Dylan J. , Liu Yuan , Lewis Colleen , Collins Hannah , Akce Mehmet , Kissick Haydn , Carthon Bradley C. , Shaib Walid L. , Alese Olatunji B. , Pillai Rathi , Steuer Conor E. , Wu Christina , Lawson David H. , Kudchadkar Ragini , El-Rayes Bassel , Master Viraj A. , Ramalingam Suresh , Owonikoko Taofeek K. , Harvey R Donald , Bilen Mehmet Asim 
Published: August 2018

Abstract
Background: Optimal biomarkers for cancer pts treated with IO are currently lacking. Markers of inflammation, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) are readily available and associated with poor outcomes. We investigated the association between these markers and CO in pts treated with IO.
Methods: We conducted a retrospective review of 90 pts with advanced cancer treated on IO-based phase I trials at the Winship Cancer Institute of Emory University between 2009-2017. Baseline NLR, MLR, and PLR were treated as continuous variables and rescaled by their own standard deviation. Overall survival (OS) was measured from the first dose of IO to date of death or hospice referral. Progression-free survival (PFS) was determined from first dose of IO to clinical or radiographic progression or death. We defined clinical benefit (CB) as complete response, partial response, or stable disease. Univariate association (UVA) and multivariable analysis (MVA) were carried out using Cox proportional hazard model or logistic regression model. Baseline covariates included race, gender, ECOG PS, # of prior therapies, Royal Marsden Hospital (RMH) risk group, IO indication, and # of metastatic sites.
Results: The median pt age was 63 years and most (59%) were men. The most common histologies were melanoma (33%) and GI cancers (22%). The majority (81%) were RMH good risk. 46% of pts had CB on IO. The median NLR, MLR, and PLR was 3.63, 0.48, and 182.65, respectively. Increased NLR, MLR, and PLR were all associated with worse OS, PFS, and chance of CB (Table 1). NLR, MLR and PLR are highly correlated to each other (Pearson correlation coefficients ≥ 0.8, all p &lt; 0.0001).
Conclusion: NLR, MLR, and PLR are strongly associated with CO in pts treated with IO. Prospective validation of these findings are warranted.
Table 1: UVA and MVA of NLR, MRL, and PLR with CO
OS PFSCBUVAMVAUVAMVAUVAMVAHR (CI)p-valueHR (CI)p-valueHR (CI)p-valueHR (CI)p-valueOR (CI)p-valueOR (CI)p-valueNLR1.37 (1.11-1.70)0.003*1.30 (1.02-1.66)0.031*1.42 (1.18-1.70)&lt;0.001*1.32 (1.06-1.63)0.011*0.47 (0.23-0.94)0.033*0.57 (0.26-1.27)0.169MLR1.38 (1.14-1.67)&lt;0.001*1.22 (0.98-1.52)0.071.39 (1.18-1.63)&lt;0.001*1.26 (1.03-1.55)0.026*0.45 (0.23-0.89)0.021*0.71 (0.32-1.57)0.398PLR1.40 (1.15-1.69)&lt;0.001*1.27 (1.03-1.56)0.027*1.40 (1.19-1.63)&lt;0.001*1.27 (1.06-1.53)0.01*0.35 (0.17-0.74)0.006*0.28 (0.11-0.67)0.005*
*statistically significant
Citation Format: Dylan J. Martini, Yuan Liu, Colleen Lewis, Hannah Collins, Mehmet Akce, Haydn Kissick, Bradley C. Carthon, Walid L. Shaib, Olatunji B. Alese, Rathi Pillai, Conor E. Steuer, Christina Wu, David H. Lawson, Ragini Kudchadkar, Bassel El-Rayes, Viraj A. Master, Suresh Ramalingam, Taofeek K. Owonikoko, R Donald Harvey, Mehmet Asim Bilen. Blood based biomarkers and association with clinical outcome (CO) in advanced stage patients (pts) treated with immunotherapy (IO) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2607.