Association of thrombocytopenia with immune checkpoint inhibitors: a large-scale pharmacovigilance analysis based on the data from FDA adverse event reporting system database

被引:3
|
作者
Liu, Geliang [1 ,2 ,3 ]
Zhang, Shuxian [1 ,3 ]
Mo, Zhuang [1 ,4 ]
Huang, Tai [1 ,3 ]
Yu, Qi [1 ,3 ]
Lu, Xuechun [1 ,3 ,5 ,6 ]
He, Peifeng [1 ,7 ]
机构
[1] Shanxi Med Univ, Shanxi Key Lab Big Data Clin Decis, Taiyuan, Peoples R China
[2] Shanxi Med Univ, Key Lab Cellular Physiol, Minist Educ, Taiyuan, Peoples R China
[3] Shanxi Med Univ, Sch Management, Taiyuan, Peoples R China
[4] Shanxi Med Univ, Sch Basic Med Sci, Taiyuan, Peoples R China
[5] China PLA Gen Hosp, Dept Hematol, Med Ctr 2, Beijing, Peoples R China
[6] Natl Ctr Clin Med Geriatr Dis, Beijing, Peoples R China
[7] Shanxi Med Univ, Inst Med Data Sci, Taiyuan, Peoples R China
关键词
immune checkpoint inhibitors; immune thrombocytopenia; immune-related adverse events; FAERS; TCGA; MTOR; GROWTH;
D O I
10.3389/fphar.2024.1407894
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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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页数:14
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