Table1_PD-1 inhibitor-based adverse events in solid tumors: A retrospective real-world study.DOCX

Background & Aims: Immune checkpoint inhibitors (ICIs) have transformed the landscape of cancer treatment, and ICI-related toxicities (i.e., immune-related adverse events (irAEs) have been reported in many clinical studies. However, the toxicity data of real-world have not been fully assessed.Methods: Patients with histologically confirmed solid tumors who had been treated with PD-1 inhibitors were included in the study. Patient data were collected from electronic medical records, including basic characteristics, data of irAEs, management and outcome. Incidences of irAEs were pooled and compared, and the risk of irAEs was also analyzed.Results: A total of 362 solid tumor patients treated with sintilimab (n = 171), camrelizumab (n = 60), toripalimab (n = 72), and pembrolizumab (n = 59) were included. In total, any grade irAEs, grade 1–2 irAEs, and grade ≥3 irAEs accounted for 47.24%, 38.67% and 8.56% of cases, reapectively. Further, 29.24% of patients discontinued immunotherapy due to irAEs, with pneumonitis being the main reason for discontinuation. By comparing the toxicity profiles between different ICIs, we found that reactive capillary haemangiomas were camrelizumab-specific. Additionally, the frequency of irAEs was association with ICIs type, the pooled incidence (standardized rate) of irAEs related to sintilimab, camrelizumab, toripalimab and pembrolizumab were 55.56% (52.81%), 48.33% (55.55%), 33.33% (29.23%) and 38.98% (38.29%), respectively. Sintilimab and camrelizumab had higher incidences of any grade and grade 1–2 than toripalimab (55.56% vs. 33.33%, p = 0.002; 48.54% vs. 25.00%, p = 0.0001) and pembrolizumab (55.56% vs. 38.98%, p = 0.0028; 48.54% vs. 25.42%, p = 0.002), while the grade ≥3 irAEs of pembrolizumab (13.56%) were approximately 1.63- to 1.93-fold higher than other ICIs, and the standardized grade ≥3 of pembrolizumab was significantly higher than that of sintilimab (13.21% vs. 7.12%, p = 0.026), especially for grade ≥3 pneumonitis. Multivariate analysis found that cumulative cycles of ICI (OR = 1.081; 95% CI: 1.023–1.142; p = 0.006), and lung cancer (OR = 1.765; 95% CI: 1.105–2.820; p = 0.017) were independent risk factors for irAEs.Conclusion: The frequency of irAEs is associated with ICI type. The pooled incidence of irAEs related to sintilimab and pneumonitis caused by pembrolizumab were higher. These data indicate the importance of having different monitoring priorities for different PD-1 inhibitors.

背景与目的：免疫检查点抑制剂（ICIs）已经彻底改变了癌症治疗的格局，且在众多临床研究中已报道了与ICIs相关的毒性（即免疫相关不良事件（irAEs））。然而，真实世界中的毒性数据尚未得到全面评估。方法：纳入了经组织学确诊的实体瘤患者，这些患者曾接受PD-1抑制剂治疗。患者数据从电子病历中收集，包括基本特征、irAEs数据、治疗措施及预后。irAEs的发生率被汇总并比较，同时irAEs的风险也被进行分析。结果：共有362名接受信迪利单抗（n = 171）、卡瑞利珠单抗（n = 60）、替雷利珠单抗（n = 72）和派姆单抗（n = 59）治疗的实体瘤患者被纳入研究。总计，任何级别的irAEs、1-2级irAEs和≥3级irAEs分别占病例的47.24%、38.67%和8.56%。此外，29.24%的患者因irAEs而中断免疫治疗，其中肺炎是中断治疗的主要原因。通过比较不同ICIs之间的毒性特征，我们发现反应性毛细血管血管瘤是卡瑞利珠单抗特有的。此外，irAEs的频率与ICIs类型相关，与信迪利单抗、卡瑞利珠单抗、替雷利珠单抗和派姆单抗相关的irAEs汇总发生率（标准化率）分别为55.56%（52.81%）、48.33%（55.55%）、33.33%（29.23%）和38.98%（38.29%）。信迪利单抗和卡瑞利珠单抗的任何级别和1-2级irAEs发生率均高于替雷利珠单抗（55.56% vs. 33.33%，p = 0.002；48.54% vs. 25.00%，p = 0.0001）和派姆单抗（55.56% vs. 38.98%，p = 0.0028；48.54% vs. 25.42%，p = 0.002），而派姆单抗的≥3级irAEs（13.56%）的频率大约是其他ICIs的1.63-至1.93倍，且派姆单抗的标准化≥3级irAEs的发生率显著高于信迪利单抗（13.21% vs. 7.12%，p = 0.026），尤其是在≥3级肺炎方面。多因素分析发现，ICIs的总治疗周期（OR = 1.081；95% CI: 1.023–1.142；p = 0.006）和肺癌（OR = 1.765；95% CI: 1.105–2.820；p = 0.017）是irAEs的独立风险因素。结论：irAEs的频率与ICIs类型相关。与信迪利单抗相关的irAEs汇总发生率以及派姆单抗引起的肺炎发生率较高。这些数据表明，针对不同的PD-1抑制剂，应采取不同的监测重点。