Mutations Associated With High-Grade irAEs in NSCLC Patients Receiving Immunotherapies
Margaret R Smith1, Yuezhu Wang1, Caroline B Dixon1
1Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC.
Clinical Lung Cancer
|August 2, 2024
Summary
Predicting high-grade immune-related adverse events (irAEs) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) is crucial. Specific tumor mutations correlate with high-grade irAEs, aiding treatment selection and monitoring.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- High-grade immune-related adverse events (irAEs) are dose-limiting and impact long-term treatment in non-small cell lung cancer (NSCLC) patients.
- Predicting high-grade irAEs can guide treatment selection and therapeutic drug monitoring.
Purpose of the Study:
- To identify specific tumor mutations associated with high-grade irAEs in NSCLC patients receiving immune checkpoint inhibitors (ICIs).
- To provide molecular guidance for optimizing NSCLC treatment strategies.
Main Methods:
- Retrospective study of 430 stage III-IV NSCLC patients treated with ICIs (with or without chemotherapy) from 2015-2022.
- Analysis of sequencing data and clinical information, including irAEs.
- Fisher's exact test used to correlate mutations with high-grade irAEs, with separate analyses for tumor subtypes.
Main Results:
- High-grade irAEs occurred in 15.2% of patients; respiratory and gastrointestinal were most common.
- Five genes (MYC, TEK, FANCA, FAM123B, MET) mutations correlated with increased risk of high-grade irAEs.
- Specific mutations (TEK, MYC, FGF19, RET, MET in adenocarcinoma; ERBB2 in squamous) were associated with high-grade irAEs in respective subtypes.
Conclusions:
- This study is the first to link specific tumor mutations to high-grade irAE incidence in NSCLC patients on ICIs.
- Findings offer molecular insights for personalized treatment selection and drug monitoring in NSCLC.
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