44 Soluble immune markers predict outcome after immune checkpoint blockade in patients with advanced cancers

<h3>Background</h3> Emergence of immune checkpoint inhibitors (ICIs) has provoked a paradigm shift in the approach to cancer therapy. However, ICIs are effective in only a small portion of patients. Biomarker-based patient selection and follow for ICIs may be important in order to optimize effectiveness. To that end, we analyzed soluble immune markers as potential biomarkers to predict responses from immunotherapy. <h3>Methods</h3> Pretreatment blood concentrations of soluble immune markers (sPD-1, sPD-L1, and sCTLA-4) before anti-PD-1/PD-L1 therapy were assessed in patients with diverse advanced/metastatic cancers, using Automated Immunoassay System HISCL^TM-5000 (Sysmex Corp., Kobe, Japan). Receiver operating characteristics (ROC) curve was utilized to determine the cutoff levels of the soluble immune markers. The Kaplan-Meier method was applied to estimate progression-free survival (PFS) and overall survival (OS), which were tested using the log-rank test. Cox regression was used to investigate the impact of the soluble immune markers, and potential predictive ability of combining the soluble immune markers was explored. The study followed the guidance of the UCSD IRB-approved study UCSD PREDICT: NCT02478931 and any interventions for which patients gave consent. <h3>Results</h3> Fifty-eight patients (diverse advanced cancers; most common, bladder and ureter (N=8) followed by colorectal cancer (N=7)) who underwent anti-PD-1 therapy (N=53) or anti-PD-L1 therapy (N=5) were analyzed. The median follow-up time was 11.8 months. High baseline sPD-L1 levels (≥230.53 pg/ml) correlated with significantly shorter OS while high levels of sPD-1 (≥139.97 pg/ml) and sCTLA-4 (≥1.495 pg/ml) correlated with longer PFS and OS in univariable analyses. In multivariable Cox regression analyses, high sPD-L1 independently correlated with shorter PFS (hazard ratio [HR] 2.83, <i>p</i> = 0.021) and OS (HR 5.68, <i>p</i> &lt;0.001); high sPD-1, with longer OS (HR 0.35, <i>p</i> = 0.035). Patient stratification by combining the soluble immune markers demonstrated that patients with high sPD-L1 and low levels of sCTLA-4 and sPD-1 had the shortest PFS (median, 1.2 months) and OS (median, 2.0 months), while those with low sPD-L1 and high levels of sCTLA-4 and sPD-1 had the longest survival, with median PFS and OS being not reached (<i>p</i> &lt; 0.001). <h3>Conclusions</h3> Soluble immune marker levels may identify patients likely to benefit from ICIs. In particular, high sPD-1 and sCTLA-4 in the presence of low sPD-L1 potentially predict longer PFS and OS after immune checkpoint blockade in the pan-cancer setting. <h3>Ethics Approval</h3> The study followed the guidance of the UCSD IRB-approved study UCSD PREDICT: NCT02478931 and any interventions for which patients gave consent.