Boucheron Tiphaine, Chiche Laurent, Penaranda Guillaume, Souquet Maxime, Pegliasco Hervé, Deturmeny Julien, Brunel Véronique, Barrière Nicolas, Arbault-Bitton Chloé, Coquet Emilie, Diaz Laetitia, Escoda Thomas
Department of Pharmacy, Hôpital Européen, Marseille, France.
Department of Internal Medicine, Hôpital Européen, Marseille, France.
Ther Clin Risk Manag. 2025 Mar 5;21:273-282. doi: 10.2147/TCRM.S479686. eCollection 2025.
Immune checkpoint inhibitors (ICIs) are responsible for causing immune-related adverse events (irAEs). The frequency and severity of irAEs depend on various factors, but the role of the molecule used remains unclear. Our aim was to assess the comparative safety profile of different programmed cell death-1 inhibitors (anti-PD1) and programmed cell death ligand-1 inhibitors (anti-PD-L1) in a real-life setting.
The occurrence of severe irAEs (grade ≥3) and their characteristics were recorded for all patients treated with anti-PD1 or anti-PD-L1, alone or in combination, at our center. Potential predictive factors for the occurrence of irAEs, particularly concerning the type of molecule, were identified by statistical analysis. Factors related to overall survival were also analyzed.
A total of 406 patients who received at least one dose of anti-PD1 (68.5%) or anti-PD-L1 (31.5%) were included, among which 60% had lung cancer. The overall frequency of the different ICIs was 51%, 17.5%, 14.3%, 12.8%, and 4.4% for pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab, respectively. Fifty-three (13%) patients experienced severe irAEs (grade 3 or 4). While there were no significant differences with regard to ICI categories (13.7% for anti-PD1 vs 11.7% for anti-PD-L1; p = 0.5878), the rates of severe irAEs were significantly different between ICIs (29.6% for nivolumab, 22.2% for avelumab, 13.8% for atezolizumab, 8.2% for pembrolizumab, and 5.8% for durvalumab; p < 0.0001). Multivariate analyses showed that treatments with nivolumab and low polymorphonuclear neutrophil level were significant risk factors for severe irAEs. The risk of early death was lower in patients who reported severe irAEs and the risk of cancer progression was greater with one of the least toxic molecules (atezolizumab).
This study highlights the differences in toxicity profile of various ICIs targeting the PD1/PD-L1 axis in real-life use, as well as the identification of possible predictive biomarkers.
免疫检查点抑制剂（ICI）可引发免疫相关不良事件（irAE）。irAE的发生率和严重程度取决于多种因素，但所用分子的作用仍不明确。我们的目的是在实际临床环境中评估不同程序性细胞死亡蛋白1抑制剂（抗PD1）和程序性细胞死亡配体1抑制剂（抗PD-L1）的相对安全性。
记录在我们中心接受抗PD1或抗PD-L1单药或联合治疗的所有患者中严重irAE（≥3级）的发生情况及其特征。通过统计分析确定irAE发生的潜在预测因素，特别是与分子类型有关的因素。还分析了与总生存期相关的因素。
共纳入406例接受至少一剂抗PD1（68.5%）或抗PD-L1（31.5%）治疗的患者，其中60%患有肺癌。帕博利珠单抗、纳武利尤单抗、阿替利珠单抗、度伐利尤单抗和阿维鲁单抗不同ICI的总体发生率分别为51%、17.5%、14.3%、12.8%和4.4%。53例（13%）患者发生严重irAE（3级或4级）。虽然ICI类别之间无显著差异（抗PD1为13.7%，抗PD-L1为11.7%；p = 0.5878），但不同ICI之间严重irAE的发生率有显著差异（纳武利尤单抗为29.6%，阿维鲁单抗为22.2%，阿替利珠单抗为13.8%，帕博利珠单抗为8.2%，度伐利尤单抗为5.8%；p < 0.0001）。多因素分析显示，纳武利尤单抗治疗和低多形核中性粒细胞水平是严重irAE的显著危险因素。报告有严重irAE的患者早期死亡风险较低，而毒性最小的分子之一（阿替利珠单抗）发生癌症进展的风险较高。
本研究强调了在实际应用中，各种靶向PD1/PD-L1轴的ICI在毒性特征方面的差异，以及确定可能的预测生物标志物。
