Guo Qian, Zhao Jin Ning, Liu Ting, Gao Jian, Guo Hui, Cheng Jing Min
School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Front Pharmacol. 2023 Jan 26;14:1057134. doi: 10.3389/fphar.2023.1057134. eCollection 2023.
Impressive advances in immunotherapy especially immune checkpoint inhibitors have made great progress in treating multiple cancers but can also cause serious even incurable immune-related adverse events, mostly found in colitis, dermatitis, hepatitis, and thyroiditis patients. Rare autoimmune hematologic toxicities have been reported in the literature, but are poorly described. Aplastic anaemia induced by immune checkpoint inhibitors is a life-threatening autoimmune disease; however, only a few cases have been reported in the literature. To characterize and evaluate Aplastic anaemia associated with different ICI regimens in public database and review the literature. We described a case series of patients experiencing Aplastic anaemia while on immune checkpoint inhibitors. We also mined the Food and Drug Administration's Adverse Event Reporting System and used reporting odds ratio, the proportional reporting ratio, the Bayesian confidence propagation neural network and the multi-item gamma Poisson shrinker algorithms to achieve the data of the suspected adverse events of Aplastic anaemia-induced by immune checkpoint inhibitors between January 2011 and June 2022. Thirteen patients with Aplastic anaemia events while on immune checkpoint inhibitors were included in our case series, and seven of them had a fatal outcome. In FAERS, a total of 38 individual case safety reports (immune checkpoint inhibitors) with different ICI regimens were retrieved, of which 25 (65.79%) were reported as monotherapy and 13 (34.2%) had a fatal outcome. The reporting odds ratio was significant for nivolumab (reporting odds ratio 3.05, 95%CI 1.73-5.38), pembrolizumab (reporting odds ratio 2.33, 95%CI 1.16-4.67), avelumab (reporting odds ratio 12.63, 95%CI 3.15-50.62) and ipilimumab/nivolumab (ROR 2.57, 95%CI 1.15-5.72). There is a significant reporting signal of Aplastic anaemia with several ICI agents. Clinicians should raise awareness and monitor this potentially fatal adverse event.
免疫疗法尤其是免疫检查点抑制剂取得了令人瞩目的进展，在多种癌症治疗中取得了巨大进步，但也可能引发严重甚至无法治愈的免疫相关不良事件，多见于结肠炎、皮炎、肝炎和甲状腺炎患者。文献中报道了罕见的自身免疫性血液学毒性，但描述甚少。免疫检查点抑制剂诱导的再生障碍性贫血是一种危及生命的自身免疫性疾病；然而，文献中仅报道了少数病例。为在公共数据库中表征和评估与不同免疫检查点抑制剂（ICI）方案相关的再生障碍性贫血，并回顾文献。我们描述了一系列在接受免疫检查点抑制剂治疗时发生再生障碍性贫血的患者病例。我们还挖掘了美国食品药品监督管理局的不良事件报告系统，并使用报告比值比、比例报告比、贝叶斯置信传播神经网络和多项伽马泊松收缩器算法，获取2011年1月至2022年6月期间免疫检查点抑制剂诱导再生障碍性贫血的疑似不良事件数据。我们的病例系列纳入了13例在接受免疫检查点抑制剂治疗时发生再生障碍性贫血事件的患者，其中7例死亡。在FDA不良事件报告系统（FAERS）中，共检索到38份不同ICI方案的个体病例安全报告（免疫检查点抑制剂），其中25份（65.79%）报告为单药治疗，13份（34.2%）有致命结局。纳武单抗的报告比值比具有统计学意义（报告比值比3.05，95%置信区间1.73 - 5.38），帕博利珠单抗（报告比值比2.33，95%置信区间1.16 - 4.67），阿维鲁单抗（报告比值比12.63，95%置信区间3.15 - 50.62）和伊匹木单抗/纳武单抗（报告比值比2.57，95%置信区间1.15 - 5.72）。几种ICI药物存在再生障碍性贫血的显著报告信号。临床医生应提高认识并监测这种潜在的致命不良事件。
