美国 FDA 批准的免疫检查点抑制剂的毒性负担模式。
Patterns of toxicity burden for FDA-approved immune checkpoint inhibitors in the United States.
机构信息
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, 201 Dowman Dr, Atlanta, GA, 30322, USA.
Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University, Atlanta, GA, 30322, USA.
出版信息
J Exp Clin Cancer Res. 2023 Jan 5;42(1):4. doi: 10.1186/s13046-022-02568-y.
BACKGROUND
Immune-related adverse events (irAEs) are a common phenomenon in cancer patients treated with immune checkpoint inhibitors (ICIs). Surprisingly, the toxicity burdens of these irAEs have not been illustrated clearly. In this study, we analyzed irAEs for seven FDA-approved ICIs in cancer treatment to show the pattern of toxicity burden among cancer patients.
METHODS
irAEs associated with seven FDA-approved ICIs, including three PD-1 inhibitors (cemiplimab, nivolumab and pembrolizumab), three PD-L1 inhibitors (atezolizumab, avelumab and durvalumab), and one CTLA-4 inhibitor (ipilimumab), were analyzed based on data from 149,303 reported cases (from January 1, 2015 to June 30, 2022) collected from the FDA Adverse Events Reporting System (FAERS) public dashboard. Proportions of serious irAEs and correlations with tumor type, age and sex were assessed via R package and GraphPad software.
RESULTS
irAEs related to anti-PD-1 ICIs required less hospital care resources compared with anti-PD-L1 and anti-CTLA-4 ICIs. Patients treated with pembrolizumab had relatively fewer serious cases. Treatment with ICIs led to the highest probability of serious irAEs in patients with lung cancer. 'Respiratory, thoracic and mediastinal disorders' and 'gastrointestinal disorders' were the two most common groups of disorders caused by the seven ICIs studied. 'Cardiac disorders' was the main type of disorders caused by these ICIs in cancer patients aged 65-85, while 'reproductive system and breast disease' was the main type of disorder in cancer patients aged 18-64. 'Respiratory, thoracic, mediastinal diseases' and 'reproductive system and breast diseases' were the main types of disorders associated with treatment with these ICIs in male and female patients, respectively.
CONCLUSION
Tissue and organ toxicities of ICIs are age and sex specific. There are risks of respiratory and urinary system toxicity in male patients and reproductive system toxicity in female patients treated with the ICIs studied. Future studies on the toxicity burden of ICIs should incorporate age and sex differences to better understand the relevance of ICI toxicity burden to human immune function to develop appropriate tumor immune and therapeutic intervention strategies.
背景
免疫相关不良反应（irAEs）是癌症患者接受免疫检查点抑制剂（ICIs）治疗的常见现象。令人惊讶的是，这些 irAEs 的毒性负担尚未得到清晰说明。在这项研究中，我们分析了七种 FDA 批准的癌症治疗用 ICI 的 irAEs，以展示癌症患者毒性负担的模式。
方法
基于 FDA 不良事件报告系统（FAERS）公共仪表板中从 2015 年 1 月 1 日至 2022 年 6 月 30 日收集的 149,303 例报告病例（报告病例）的数据，分析了与七种 FDA 批准的 ICI 相关的 irAEs，包括三种 PD-1 抑制剂（cemiplimab、nivolumab 和 pembrolizumab）、三种 PD-L1 抑制剂（atezolizumab、avelumab 和 durvalumab）和一种 CTLA-4 抑制剂（ipilimumab）。通过 R 包和 GraphPad 软件评估严重 irAEs 的比例以及与肿瘤类型、年龄和性别之间的相关性。
结果
与抗 PD-L1 和抗 CTLA-4 ICI 相比，抗 PD-1 ICI 相关的 irAEs 需要较少的医院资源。接受 pembrolizumab 治疗的患者严重病例相对较少。ICI 治疗导致肺癌患者发生严重 irAEs 的概率最高。“呼吸、胸部和纵隔疾病”和“胃肠道疾病”是这七种 ICI 研究引起的两个最常见的疾病组。在 65-85 岁的癌症患者中，“心脏疾病”是这些 ICI 引起的主要疾病类型，而在 18-64 岁的癌症患者中，“生殖系统和乳房疾病”是主要疾病类型。“呼吸、胸部和纵隔疾病”和“生殖系统和乳房疾病”分别是男性和女性患者接受这些 ICI 治疗相关的主要疾病类型。
结论
ICI 的组织和器官毒性具有年龄和性别特异性。接受研究中的 ICI 治疗的男性患者有发生呼吸系统和泌尿系统毒性的风险，女性患者有发生生殖系统毒性的风险。未来对 ICI 毒性负担的研究应纳入年龄和性别差异，以更好地了解 ICI 毒性负担与人类免疫功能的相关性，从而制定适当的肿瘤免疫和治疗干预策略。
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