SYSTEMATIC REVIEW article
Front. Med.
Sec. Pulmonary Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1614442
Incidence of Pneumonitis with CTLA-4 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Provisionally accepted
- 1Department of Urology, First Affiliated Hospital, Dalian Medical University, Dalian, China
- 2Second People’s Hospital of Yibin, Yibin, China
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Background: CTLA-4 inhibitors, such as tremelimumab and ipilimumab, are increasingly used in the treatment of non-small cell lung cancer (NSCLC). This meta-analysis aims to evaluate the incidence of pneumonitis associated with these inhibitors and explore potential differences between individual agents. Methods: A systematic search across three online databases identified 911 records. After screening for duplicates and irrelevant articles, 9 studies with a total of 4,164 patients were included. Risk of bias was assessed using the Cochrane "Risk of Bias" tool. Pneumonitis incidence was analyzed using a random-effects model.The overall incidence of any-grade pneumonitis was 4.0% (95% CI [2.2%, 5.8%]).High-grade pneumonitis occurred in 1.6% (95% CI [0.5%, 2.6%]). Subgroup analysis revealed that tremelimumab was associated with a higher incidence of both any-grade (8.0% vs. 2.0%) and high-grade (3.0% vs. 1.0%) pneumonitis compared to ipilimumab. In a comparison with a control group, patients receiving CTLA-4 inhibitors had a significantly higher incidence of any-grade pneumonitis (OR = 3.00, 95% CI [1.60, 5.64], p < 0.01). However, the difference in high-grade pneumonitis between the two groups was not statistically significant (RR = 1.79, 95% CI [0.83, 3.85], p = 0.14).This meta-analysis indicates that CTLA-4 inhibitors are associated with a higher incidence of pneumonitis in NSCLC patients, particularly with tremelimumab. These findings underline the importance of close monitoring for pneumonitis in patients receiving CTLA-4 1 Li et al.inhibitors, especially tremelimumab, and suggest the need for further research into prevention and management strategies.
Keywords: CTLA-4 inhibitors, Non-small cell lung cancer (NSCLC), Meta-analysis, Pneumonitis, Immune-related adverse events, Tremelimumab, ipilimumab, immune checkpoint inhibitors
Received: 18 Apr 2025; Accepted: 01 Jul 2025.
Copyright: © 2025 AL-DANAKH, Li, Xiong, Peng, Yang, Fan and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yanlin Zhang, Second People’s Hospital of Yibin, Yibin, 644000, China
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