Peripheral Blood Markers Identify Risk of Immune‐Related Toxicity in Advanced Non‐Small Cell Lung Cancer Treated with Immune‐Checkpoint Inhibitors

• Published in: The oncologist (Dayton, Ohio) Ohio), 2019-08, Vol.24 (8), p.1128-1136
• Main Authors: Pavan, Alberto, Calvetti, Lorenzo, Dal Maso, Alessandro, Attili, Ilaria, Del Bianco, Paola, Pasello, Giulia, Guarneri, Valentina, Aprile, Giuseppe, Conte, PierFranco, Bonanno, Laura
• Format: Article
• Language: English
• Subjects: Immune‐related adverse events; Immunotherapy; Lung Cancer; Neutrophil‐to‐lymphocyte ratio; Platelet‐to‐lymphocyte ratio; Predictive markers
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2018-0563

Background Immune‐checkpoint inhibitors (ICIs) are now standard of care for advanced non‐small cell lung cancer (NSCLC). Unfortunately, many patients experience immune‐related adverse events (irAEs), which are usually mild and reversible, but they require timely management and may be life threatening. No predictive markers of irAEs are available. Materials and Methods The neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) were evaluated in patients with NSCLC consecutively treated with ICIs. Prespecified cutoff values of NLR and PLR were used and related to outcome and onset of irAEs. A control group of patients with advanced NSCLC not receiving ICIs was included. Results The study included 184 patients: 26 (14.1%) received pembrolizumab upfront, and 142 (77%) received ICIs (pembrolizumab, nivolumab or atezolizumab) after one or more lines of chemotherapy. The median number of ICIs cycles was six (range, 1–61). The median progression‐free survival and overall survival were 4.8 (95% CI, 3.4–6.3) and 20.6 (95% CI, 14.7–26.5) months, respectively. Sixty patients (32.6%) developed irAEs, mainly grade 1–2 (65.0%), causing ICI interruption in 46 cases (25.0%). Low NLR and low PLR at baseline were significantly associated with the development of irAEs (odds ratio [OR], 2.2; p = .018 and OR, 2.8; p = .003, respectively). Multivariate analyses confirmed PLR as independent predictive marker of irAEs (OR, 2.3; p = .020). Conclusion NLR and PLR may predict the appearance of irAEs in non‐oncogene‐addicted aNSCLC, although this conclusion warrants prospective validation. Implications for Practice This study was designed to investigate the role of blood biomarkers in predicting the occurrence of immune‐related adverse events (irAEs) in patients with advanced non‐small cell lung cancer receiving immunotherapy. The results of the study suggest a potential predictive role of neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio as markers for irAE development in this category of patients. These data provide rationale for an easy and feasible application to be validated in clinical practice. 摘要 背景。免疫检查点抑制剂 (ICI) 药物目前是治疗晚期非小细胞肺癌 (NSCLC) 的标准药物。不幸的是，许多患者会出现免疫相关不良事件 (irAE)，虽然此类事件通常并不严重而且可逆，但需要及时治疗而且可能会危及生命。目前还没有 irAE 的预测标志物。 材料和方法。评估连续接受 ICI 治疗的 NSCLC 患者的中性粒细胞淋巴细胞比 (NLR) 和血小板淋巴细胞比 (PLR)。使用预先指定的 NLR 和 PLR 临界值，该值与 irAE 结局和发病相关。对照组选择未接受 ICI 治疗的晚期 NSCLC 患者。 结果。研究包括 184 名患者:26 例 (14.1%) 预先接受帕博利珠单抗 (Pembrolizumab) 治疗，142 例 (77%) 在经过一线或多线化疗之后接受 ICI(帕博