Immune checkpoint inhibitors and myocarditis in advanced non-small cell lung cancer: a nationwide cohort study

Abstract Objective Evidence suggests immune checkpoint inhibitor (ICI) can increase the risk of myocarditis. We investigated it in a large national cohort in China. Methods Patients with stage IIIB-IV non-small cell lung cancer (NSCLC) using data from China's National Anti-Tumor Drug Surveillan...

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Main Authors: Fu-Xiao Li, Jia-Xin Cai, Ji-Bin Li, Kong-Jia Luo, Shi-Yu Wang, Wei-Hua Meng, Feng Sha, Zhi-Rong Yang, Allan Hackshaw, Jin-Ling Tang
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Cardio-Oncology
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Online Access:https://doi.org/10.1186/s40959-025-00325-6
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author Fu-Xiao Li
Jia-Xin Cai
Ji-Bin Li
Kong-Jia Luo
Shi-Yu Wang
Wei-Hua Meng
Feng Sha
Zhi-Rong Yang
Allan Hackshaw
Jin-Ling Tang
author_facet Fu-Xiao Li
Jia-Xin Cai
Ji-Bin Li
Kong-Jia Luo
Shi-Yu Wang
Wei-Hua Meng
Feng Sha
Zhi-Rong Yang
Allan Hackshaw
Jin-Ling Tang
author_sort Fu-Xiao Li
collection DOAJ
description Abstract Objective Evidence suggests immune checkpoint inhibitor (ICI) can increase the risk of myocarditis. We investigated it in a large national cohort in China. Methods Patients with stage IIIB-IV non-small cell lung cancer (NSCLC) using data from China's National Anti-Tumor Drug Surveillance System between January 2013 and December 2021. Exposure density sampling was applied to control for immortal time bias. Multivariate Cox regression with time-dependent exposures was used to examine the association between ICI therapy and the incidence of myocarditis while controlling for confounders. Results 55,219 patients were included. The median age was 61 years, and 62% were males. At one-year follow-up (median 335 days), there were 26 cases of myocarditis among ICI users and 28 cases among ICI non-users (a cumulative incidence of 4.8 and 0.6 per 1000 person-years respectively). The adjusted hazard ratio (HR) of myocarditis for ICI users was 7.41 (95% confidence interval [CI]: 3.29–16.67). For programmed cell death protein 1 inhibitor users the HR was 8.39 (95% CI: 3.56–19.77). No significant interactions were observed in subgroup analysis. The results remained unchanged in sensitivity analyses. Conclusions This study showed that ICI therapy considerably increased the risk of myocarditis, supporting the need for closer monitoring of patients receiving ICI therapies.
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spelling doaj-art-d7a7db164e324b4a8b5979d7eedd518e2025-08-20T02:25:41ZengBMCCardio-Oncology2057-38042025-03-0111111110.1186/s40959-025-00325-6Immune checkpoint inhibitors and myocarditis in advanced non-small cell lung cancer: a nationwide cohort studyFu-Xiao Li0Jia-Xin Cai1Ji-Bin Li2Kong-Jia Luo3Shi-Yu Wang4Wei-Hua Meng5Feng Sha6Zhi-Rong Yang7Allan Hackshaw8Jin-Ling Tang9Department of Computational Biology and Medical Big Data, Shenzhen University of Advanced TechnologyDepartment of Computational Biology and Medical Big Data, Shenzhen University of Advanced TechnologyDepartment of Clinical Research, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineState Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer CenterShenzhen Institute of Advanced Technology, Chinese Academy of SciencesNottingham Ningbo China Beacons of Excellence Research and Innovation Institute, University of Nottingham Ningbo ChinaShenzhen Institute of Advanced Technology, Chinese Academy of SciencesDepartment of Computational Biology and Medical Big Data, Shenzhen University of Advanced TechnologyCRUK & UCL Trials Centre, University College LondonDepartment of Computational Biology and Medical Big Data, Shenzhen University of Advanced TechnologyAbstract Objective Evidence suggests immune checkpoint inhibitor (ICI) can increase the risk of myocarditis. We investigated it in a large national cohort in China. Methods Patients with stage IIIB-IV non-small cell lung cancer (NSCLC) using data from China's National Anti-Tumor Drug Surveillance System between January 2013 and December 2021. Exposure density sampling was applied to control for immortal time bias. Multivariate Cox regression with time-dependent exposures was used to examine the association between ICI therapy and the incidence of myocarditis while controlling for confounders. Results 55,219 patients were included. The median age was 61 years, and 62% were males. At one-year follow-up (median 335 days), there were 26 cases of myocarditis among ICI users and 28 cases among ICI non-users (a cumulative incidence of 4.8 and 0.6 per 1000 person-years respectively). The adjusted hazard ratio (HR) of myocarditis for ICI users was 7.41 (95% confidence interval [CI]: 3.29–16.67). For programmed cell death protein 1 inhibitor users the HR was 8.39 (95% CI: 3.56–19.77). No significant interactions were observed in subgroup analysis. The results remained unchanged in sensitivity analyses. Conclusions This study showed that ICI therapy considerably increased the risk of myocarditis, supporting the need for closer monitoring of patients receiving ICI therapies.https://doi.org/10.1186/s40959-025-00325-6Non-small cell lung cancerImmune checkpoint inhibitorMyocarditisCohort studyReal-world evidenceCardiotoxicity
spellingShingle Fu-Xiao Li
Jia-Xin Cai
Ji-Bin Li
Kong-Jia Luo
Shi-Yu Wang
Wei-Hua Meng
Feng Sha
Zhi-Rong Yang
Allan Hackshaw
Jin-Ling Tang
Immune checkpoint inhibitors and myocarditis in advanced non-small cell lung cancer: a nationwide cohort study
Cardio-Oncology
Non-small cell lung cancer
Immune checkpoint inhibitor
Myocarditis
Cohort study
Real-world evidence
Cardiotoxicity
title Immune checkpoint inhibitors and myocarditis in advanced non-small cell lung cancer: a nationwide cohort study
title_full Immune checkpoint inhibitors and myocarditis in advanced non-small cell lung cancer: a nationwide cohort study
title_fullStr Immune checkpoint inhibitors and myocarditis in advanced non-small cell lung cancer: a nationwide cohort study
title_full_unstemmed Immune checkpoint inhibitors and myocarditis in advanced non-small cell lung cancer: a nationwide cohort study
title_short Immune checkpoint inhibitors and myocarditis in advanced non-small cell lung cancer: a nationwide cohort study
title_sort immune checkpoint inhibitors and myocarditis in advanced non small cell lung cancer a nationwide cohort study
topic Non-small cell lung cancer
Immune checkpoint inhibitor
Myocarditis
Cohort study
Real-world evidence
Cardiotoxicity
url https://doi.org/10.1186/s40959-025-00325-6
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