Factors Predictive of Primary Resistance to Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer

Introduction: Primary resistance to immune checkpoint inhibitors (ICI) is observed in routine clinical practice. We sought to determine factors predictive of primary resistance to ICI monotherapy, defined by the Society for Immunotherapy of Cancer (SITC) as progression within 6 months of ICI treatment with patients receiving at least 6 weeks of ICI monotherapy, in patients with advanced non-small-cell lung cancer (NSCLC).

Method: Patients with stage IV NSCLC treated with at least 6 weeks of single-agent ICI at two tertiary hospitals in Singapore were included. A multivariate logistic regression model was utilised to elucidate factors predictive of primary resistance to ICI.

Results: Of the 108 eligible patients, 59 (54.6%) experienced primary resistance. The majority were male (65.7%), smokers (66.3%), Chinese (79.6%), had adenocarcinoma (76.9%), received Pembrolizumab (55.6%) and received immunotherapy treatment in the later line setting (≥2 lines) (61.1%). Female gender (aOR = 3.16, p = 0.041), a sixth-week neutrophil-to-lymphocyte ratio (NLR) of ≥3) (aOR = 3.454, p = 0.037) and a later line of immunotherapy treatment (≥2 lines) (aOR = 2.676, p = 0.040) were factors predictive of primary resistance to ICI monotherapy in patients with advanced NSCLC.

Conclusions: Using SITC criteria, an elevated NLR (≥3) at 6 weeks, female gender and a later line of immunotherapy treatment (≥2 lines) were predictive factors of developing primary resistance to ICI monotherapy in patients with advanced NSCLC.