Abstract 1305P
Background
Different groups have recently revealed the usefulness of immune cell quantification in peripheral blood to predict response to immune checkpoint inhibitors (ICI). Our team found an association between CD4+ CD27- CD28- T cells and response to ICI in pretreated NSCLC patients (Zuazo M, 2019), however these findings were not applicable in frontline ICI. We evaluated a cohort of untreated NSCLC patients receiving ICI alone or in combination with chemotherapy (CT+IT).
Methods
PBMCs from 39 patients were obtained from fresh peripheral blood immediately before treatment. The proportions of cell subpopulations have been studied by flow cytometry according to the expression of T cell and myeloid markers. Cocultures of patient's lymphocytes with a target cancer cell line (A549-OKT3) using real time cell analysis (RTCA) have been performed to evaluate anti-tumor capacity.
Results
In patients receiving ICI as single agent, disease control (DC) longer than 6 months was associated with lower levels of low density neutrophils (LDN); 1.17% vs 19.7% (p = 0.01). A threshold of 7.08% LDN identified patients with DC < 6 months with a 80% sensitivity and 80% specificity (ROC analysis AUC 0.880, p = 0.004). Patients with > 7.08% of LDNs had significantly shorter PFS (13.5 vs 74.8 weeks, p = 0.012). LDN levels were not associated with response in patients treated with chemo-immunotherapy combination (ROC analysis AUC 0.486, p=0.935), nor in an independent cohort of NSCLC patients receiving immunotherapy as second-line treatment (p=0.230). Using RTCA, lymphocytes from patients and from healthy donors had equal antitumor capacity regardless of LDN levels, suggesting that other factors apart from T cell functionality are influencing clinical responses.
Conclusions
High levels of LDNs are associated to primary resistance to ICI monotherapy, while some of these patients can respond to CT+IT, indicating a predictive value. This finding suggest that some NSCLC patients with PD-L1 expression ≥50% might benefit from CT+IT.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Oncoimmunology Group, Navarrabiomed.
Funding
Asociación Española Contra el Cáncer (AECC), Instituto de Salud Carlos III (ISCIII).
Disclosure
H. Arasanz: Financial Interests, Personal, Advisory Role: AstraZeneca. All other authors have declared no conflicts of interest.