| アブストラクト | Introduction: An increasing number of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been reported during clinical treatment. We aimed to explore the clinical characteristics of patients with ICIs-induced ITP under different therapeutic strategies based on the FAERS database and explore the potential biological mechanisms in combination with TCGA pan-cancer data. Methods: Data from FAERS were collected for ICIs adverse reactions between January 2012 and December 2022. Disproportionality analysis identified ICIs-induced ITP in the FAERS database using the reporting odds ratio (ROR), proportional reporting ratio (PRP), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker algorithms (MGPS). The potential biological mechanisms underlying ITP induced by ICIs were examined using TCGA transcriptome data on cancers. Results: In the FAERS, 345 ICIs-induced ITP reports were retrieved, wherein 290 (84.06%) and 55 (15.94%) were reported as monotherapy and combination therapy, respectively. The median age of the reported patients with ICIs-induced ITP was 69 years (IQR 60-76), of which 62 (18%) died and 47 (13.6%) had a life-threatening outcome. The majority of reported indications were lung, skin, and bladder cancers, and the median time to ITP after dosing was 42 days (IQR 17-135), with 64 patients (43.5%) experiencing ITP within 30 days of dosing and 88 patients experiencing ITP in less than 2 months (59.9%). The occurrence of ICIs-induced ITP may be associated with ICIs-induced dysregulation of the mTORC1 signaling pathway and megakaryocyte dysfunction. Conclusion: There were significant reporting signals for ITP with nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab/ipilimumab, and pembrolizumab/ipilimumab. Patients treated with anti-PD-1 in combination with anti-CTLA-4 are more likely to have an increased risk of ICIs-induced ITP. Patients with melanoma are at a higher risk of developing ITP when treated with ICI and should be closely monitored for this risk within 60 days of treatment. The potential biological mechanism of ICIs-induced ITP may be related to the dysfunction of megakaryocyte autophagy through the overactivation of the mTOR-related signaling pathway. This study provides a comprehensive understanding of ICIs-induced ITP. Clinicians should pay attention to this potentially fatal adverse reaction. |
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| ジャーナル名 | Frontiers in pharmacology |
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| 投稿日 | 2024/7/2 |
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| 投稿者 | Liu, Geliang; Zhang, Shuxian; Mo, Zhuang; Huang, Tai; Yu, Qi; Lu, Xuechun; He, Peifeng |
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| 組織名 | Shanxi Key Laboratory of Big Data for Clinical Decision, Shanxi Medical;University, Taiyuan, China.;Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical;School of Management, Shanxi Medical University, Taiyuan, China.;School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China.;Department of Hematology, The Second Medical Center of the China PLA General;Hospital and National Center for Clinical Medicine of Geriatric Diseases,;Beijing, China.;Institute of Medical Data Sciences, Shanxi Medical University, Taiyuan, China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/38953101/ |
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