简介：在临床治疗过程中，越来越多的免疫检查点抑制剂（ICIs）引起的免疫相关不良事件（irAE）被报道。我们旨在基于FAERS数据库探讨不同治疗策略下ICIs诱导的ITP患者的临床特征，并结合TCGA泛癌数据探讨潜在的生物学机制。方法：收集 FAERS 2012 年 1 月至 2022 年 12 月期间 ICI 不良反应的数据。不成比例分析使用报告优势比 (ROR)、比例报告比 (PRP)、贝叶斯置信传播神经网络在 FAERS 数据库中识别 ICI 诱发的 ITP （BCPNN）和多项伽玛泊松收缩算法（MGPS）。使用癌症的 TCGA 转录组数据检查了 ICI 诱导 ITP 的潜在生物学机制。结果：FAERS 共检索到 345 份 ICI 诱发 ITP 报告，其中单药治疗 290 份（84.06%），联合治疗 55 份（15.94%）。报告的 ICI 诱发 ITP 患者的中位年龄为 69 岁（IQR 60-76），其中 62 例（18%）死亡，47 例（13.6%）出现危及生命的结果。报告的大多数适应症是肺癌、皮肤癌和膀胱癌，给药后出现 ITP 的中位时间为 42 天 (IQR 17-135)，其中 64 名患者 (43.5%) 在给药后 30 天内出现 ITP，88 名患者出现 ITP不到 2 个月即可发生 ITP (59.9%)。 ICIs诱导的ITP的发生可能与ICIs诱导的mTORC1信号通路失调和巨核细胞功能障碍有关。结论：纳武单抗、帕博利珠单抗、西米普利单抗、阿特珠单抗、avelumab、durvalumab、伊匹单抗、纳武单抗/伊匹单抗和帕博利珠单抗/伊匹单抗对 ITP 有显着的报告信号。接受抗 PD-1 联合抗 CTLA-4 治疗的患者发生 ICI 诱发 ITP 的风险更有可能增加。黑色素瘤患者在接受 ICI 治疗时发生 ITP 的风险较高，应在治疗后 60 天内密切监测这种风险。 ICIs诱导ITP的潜在生物学机制可能与mTOR相关信号通路过度激活导致巨核细胞自噬功能障碍有关。这项研究提供了对 ICI 诱导的 ITP 的全面了解。临床医生应注意这种潜在的致命不良反应。版权所有 © 2024 Liu、Zhang、Mo、Huang、Yu、Lu 和 He。

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.Copyright © 2024 Liu, Zhang, Mo, Huang, Yu, Lu and He.