Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC.
Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC.
Clin Lung Cancer. 2024 Dec;25(8):e379-e388. doi: 10.1016/j.cllc.2024.07.003. Epub 2024 Jul 14.
Compared to low-grade irAEs, high-grade irAEs are more often dose-limiting and can alter the long-term treatment options for a patient. Predicting the incidence of high-grade irAEs would help with treatment selection and therapeutic drug monitoring.
We performed a retrospective study of 430 stage III and IV patients with non-small cell lung cancer (NSCLC) who received an immune checkpoint inhibitor (ICI), either with or without chemotherapy, at a single comprehensive cancer center from 2015 to 2022. The study team retrieved sequencing data and complete clinical information, including detailed irAEs medical records. Fisher's exact test was used to determine the association between mutations and the presence or absence of high-grade irAEs. Patients were analyzed separately based on tumor subtypes and sequencing platforms.
High-grade and low-grade irAEs occurred in 15.2% and 46.2% of patients, respectively. Respiratory and gastrointestinal irAEs were the 2 most common irAEs. The distribution of patients with or without irAEs was similar between ICI and ICI+chemotherapy-treated patients. By analyzing the mutation data, we identified 5 genes (MYC, TEK, FANCA, FAM123B, and MET) with mutations that were correlated with an increased risk of high-grade irAEs. For the adenocarcinoma subtype, mutations in TEK, MYC, FGF19, RET, and MET were associated with high-grade irAEs; while for the squamous subtype, ERBB2 mutations were associated with high-grade irAEs.
This study is the first to demonstrate that specific tumor mutations correlate with the incidence of high-grade irAEs in patients with NSCLC treated with an ICI, providing molecular guidance for treatment selection and drug monitoring.
与低级别免疫相关不良事件（irAE）相比，高级别 irAE 更常导致剂量限制，并可能改变患者的长期治疗选择。预测高级别 irAE 的发生率有助于治疗选择和治疗药物监测。
我们对 2015 年至 2022 年期间在一家综合性癌症中心接受免疫检查点抑制剂（ICI）治疗的 430 例 III 期和 IV 期非小细胞肺癌（NSCLC）患者进行了回顾性研究，ICI 治疗或联合化疗。研究小组检索了测序数据和完整的临床信息，包括详细的 irAE 病历。Fisher 确切检验用于确定突变与高级别 irAE 的存在或缺失之间的关联。根据肿瘤亚型和测序平台，分别对患者进行分析。
高级别和低级别 irAE 分别发生在 15.2%和 46.2%的患者中。呼吸系统和胃肠道 irAE 是最常见的 2 种 irAE。ICI 和 ICI+化疗治疗患者的 irAE 发生率相似。通过分析突变数据，我们确定了 5 个与高级别 irAE 风险增加相关的基因突变（MYC、TEK、FANCA、FAM123B 和 MET）。对于腺癌亚型，TEK、MYC、FGF19、RET 和 MET 基因突变与高级别 irAE 相关；而对于鳞状细胞癌亚型，ERBB2 基因突变与高级别 irAE 相关。
本研究首次证明，特定的肿瘤突变与 NSCLC 患者接受 ICI 治疗后高级别 irAE 的发生率相关，为治疗选择和药物监测提供了分子指导。
