Huang Yiqing, Zhao Joseph J, Soon Yu Yang, Kee Adrian, Tay Sen Hee, Aminkeng Folefac, Ang Yvonne, Wong Alvin S C, Bharwani Lavina D, Goh Boon Cher, Soo Ross A
Department of Haematology-Oncology, National University Cancer Institute Singapore, Singapore 119074, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.
Cancers (Basel). 2023 May 12;15(10):2733. doi: 10.3390/cancers15102733.
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).
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.
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, = 0.041), a sixth-week neutrophil-to-lymphocyte ratio (NLR) of ≥3) (aOR = 3.454, = 0.037) and a later line of immunotherapy treatment (≥2 lines) (aOR = 2.676, = 0.040) were factors predictive of primary resistance to ICI monotherapy in patients with advanced NSCLC.
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.
在常规临床实践中观察到对免疫检查点抑制剂（ICI）的原发性耐药。我们试图确定晚期非小细胞肺癌（NSCLC）患者中对ICI单药原发性耐药的预测因素，癌症免疫治疗学会（SITC）将其定义为接受至少6周ICI单药治疗的患者在ICI治疗6个月内出现疾病进展。
纳入在新加坡两家三级医院接受至少6周单药ICI治疗的IV期NSCLC患者。采用多因素逻辑回归模型阐明对ICI原发性耐药的预测因素。
108例符合条件的患者中，59例（54.6%）出现原发性耐药。大多数为男性（65.7%）、吸烟者（66.3%）、华裔（79.6%），患有腺癌（76.9%），接受帕博利珠单抗治疗（55.6%）且在晚期治疗线（≥2线）接受免疫治疗（61.1%）。女性（调整后比值比[aOR]=3.16，P=0.041）、第6周中性粒细胞与淋巴细胞比值（NLR）≥3（aOR=3.454，P=0.037）以及晚期免疫治疗线（≥2线）（aOR=2.676，P=0.040）是晚期NSCLC患者对ICI单药原发性耐药的预测因素。
采用SITC标准，6周时NLR升高（≥3）、女性以及晚期免疫治疗线（≥2线）是晚期NSCLC患者对ICI单药产生原发性耐药的预测因素。
