Proffered Paper - Translational research Proffered Paper session

1929O - Soluble PD-L1 and circulating CD8+PD1+ and NK cells enclose a highly prognostic and predictive immune effector score in immunotherapy treated NSCLC patients

Presentation Number
1929O
Lecture Time
14:37 - 14:49
Speakers
  • Giulia Mazzaschi (Parma, Italy)
Room
Channel 2
Date
19.09.2020
Time
14:25 - 16:05

Abstract

Background

Upfront criteria to foresee immune checkpoint inhibitors (ICI) efficacy are far from being identified. Thus, we integrated blood descriptors of pro-inflammatory/immunosuppressive or effective anti-tumor response to define predictive immune profiles in ICI-treated advanced NSCLC.

Methods

Peripheral blood (PB) was prospectively collected at baseline from 109 consecutive NSCLC patients undergoing ICI as first or more line treatment. Soluble PD-L1 (sPD-L1) (immunoassay), CD8+PD1+ and NK cells (FACS) were assessed and integrated to generate an Immune effector Score (IeffS). Lung Immune Prognostic Index (LIPI) was also computed by LDH levels and derived Neutrophil-to-Lymphocyte Ratio (dNLR). All these parameters were correlated with survival outcome and response to treatment.

Results

High sPD-L1 and low PB number of CD8+PD1+ and NK cells, individually had a negative impact on both PFS (P<0.001) and OS (P<0.01) as well as on ICI-response (P<0.05). Thus, sPD-L1high, CD8+PD1+low and NKlow were considered as risk factors encompassing IeffS, whose prognostic power outperformed that of single features and slightly exceeded that of LIPI. Accordingly, the absence of these pre-determined risk factors portrayed a favorable IeffS able to identify NSCLC patients with significantly prolonged PFS (median NR vs 2.3 months, P<0.001) and OS (median NR vs 4.1, P<0.001) and greater benefit from ICI (P<0.01). We then combined each individual risk parameter composing IeffS and LIPI (LDHhigh, dNLRhigh), thus defining three distinct prognostic classes: 0-1 vs 2-3 vs ≥ 4 risk factors. A remarkable impact of IeffS-LIPI integration was documented in terms of survival outcome (PFS: HR, 4.61; 95% CI, 2.32-9.18; P<0.001; OS: HR, 4.03; 95% CI, 1.91-8.67; P<0.001) and response to ICI (ROC curve AUC=0.90, 95% CI 0.81-0.97, P<0.001).

Conclusions

Composite risk models based on blood parameters featuring the tumor-host interaction might provide non-invasive prognostic and predictive scores in ICI-treated advanced NSCLC patients.

Legal entity responsible for the study

University Hospital of Parma.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Collapse