Abstract 1287P
Background
The use of tumor tissue biomarkers of response to cancer immunotherapy is very limited. We have prospectively explored whether immunophenotype of peripheral blood cells (PBCs) of advanced NSCLC patients (pts) is associated with anti-PD-1 immunotherapy efficacy.
Methods
We studied 108 immune subpopulations in PBCs in a cohort of NSCLC pts, including subsets of T, NK and B cells, monocytes and dendritic cells, prior to the start of single-agent nivolumab or pembrolizumab treatment. As a control group, we also studied pts with advanced cancer before non-immunotherapeutic treatment initiation. The level of immune subpopulations was correlated with clinical-demographic characteristics and treatment outcome in terms of overall (OS) and progression-free survival (PFS). We performed a survival analysis for each individual subpopulation in each of the two cohorts, in which censorship and confounding clinical-demographic variables were included in a multivariate analysis.
Results
NSCLC group were 39 pts, control: 40. Median age: 69.5 in NSCLC, 68 years in control (p=0.73); sex: 3 females in NSCLC, 16 in control (p<0.05). 20 pts received pembrolizumab and 19 nivolumab in NSCLC cohort. High levels of the immune subpopulation were defined as levels above the 55th percentile and low levels, below the 45th. 4 subpopulations showed a differential predictive pattern in the study cohort (NSCLC). Low baseline levels of CD3+CD4+CCR9+ (OS: 35.9 vs 15.7 months, HR 0.16, p=0.003; PFS: NR-not reached- vs 2.6, HR 0.3, p=0.019), CD3+CD4+CCR10+ (OS: NR vs 22.0 months, HR 0.10, p=0.003; PFS: NR vs 8.5 PFS, HR 0.54, p=0.2) and CD3+CD8+CXCR4+ (OS: NR vs 22.0 months, HR 0.29, p=0.02; PFS: 14.2 vs 5.0 PFS, HR 0.43, p=0.12); and high levels of CD56+Tie2+ (OS: NR vs 25.9 months, HR 2.1 p = 0.17; PFS: NR vs 6.9, HR 5.0, p=0.01) demonstrated benefit. In the control cohort, none of these subpopulations had a comparable behavior.
Conclusions
Low baseline levels of helper T cells (CD4+) expressing CCR9 or CCR10, and cytotoxic T cells (CD8+) expressing CXCR4, as well as a high baseline levels of NKs cells (CD56+) expressing Tie2, define an immune profile in PBCs that is associated with better outcome to anti-PD-1 antibodies in NSCLC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Instituto de Salud Carlos III, Ministerio de Economía y Competitividad.
Disclosure
All authors have declared no conflicts of interest.