6533b836fe1ef96bd12a12ec

RESEARCH PRODUCT

Soluble biomarker signature to predict outcome of patients with non-small-cell lung cancer (NSCLC) treated with anti-PD1/PDL1 monoclonal antibodies.

subject

description

e20685 Background: Immunotherapy with anti-PD1/PDL1 monoclonal antibodies has become the second line standard treatment for most patients diagnosed of advanced Non-Small-Cell lung cancer (NSCLC). The aim of this study is to assess the utility of circulating biomarkers such as sPDL1, sPDL2, sCD137, sIDO, sTIM3, sCD28, sCD27, sCTLA4, sHVEM, sLAG3, sCD80 and sGITR for predicting efficacy of immunotherapy with anti-PD1/PDL1 therapies. Methods: Blood samples were collected before treatment from 50 NSCLC patients who received anti PD1/PDL1 therapies (second line). Plasma biomarkers´ levels were measured by Multiplex bead-based assays. Continuous variables were categorized using the median as a cut-off. Non parametric test were used for correlations between analytical variables and clinical-pathological parameters and response rate analysis. For survival analysis (progression free survival-PFS and overall survival-OS) Kaplan Meier curves and long-rank test were performed. Results: 50 patients met inclusion criteria. Biomarkers associated with better outcome in terms of Response Rate or PFS were sPDL1, sIDO, sCD137 and sGITR. Median plasma levels of sPDL1, sCD137, sIDO and sGITR were 80.5, 168.7, 64.92s and 114.43 ng/ml respectively. ORR was higher in patients with high levels of CD137 (75 vs 25%, p = 0.28), GITR (83.3 vs 16.7%, p = 0.009) and sPDL1 (66.7 vs 33.3%, p = 0.07). Median PFS was significantly higher for patients with high sPDL1 levels (NR vs 3 months, p = 0.017), and there was a favourable trend for patients with higher serum levels of CD137 (NR vs 5.07, p = 0.11), sIDO (NR vs 5.57 months, p = 0.08); and sGITR (14.33 vs 5.57 months, p = 0.16). Combination of these biomarkers allowed the identification of three groups: group1 (0-1 positive biomarker), group2 (2 positive biomarkers) and group 3 (3 or 4 positive biomarkers), with significant differences in ORR (8.3 vs 25 vs 66.7%, p = 0.01), PFS (median 3.2, 1.1 and NR months, p = 0.01) and OS (median 2.3, 5.0 and NR months, p = 0.02). Conclusions: Circulating immune markers can be reliable detected in plasma of advanced NSCLC patients. In patients treated with anti-PD1 antibodies. sCD137, sIDO, sGITR and sPDL1 seem to be related to the degree of response or PFS. Combination of these biomarkers might be helpful to predict efficacy of immunotherapy treatment.