Abstract

Background

Immunotherapy with checkpoint inhibition has gained high importance for oncological treatments with benefits in overall survival (OS). However these drugs are not harmless, and immune related adverse events (irAE) have been reported. We pretend to evaluate which patients (pts) are in risk for developing these.

Methods

Retrospective evaluation of all pts treated with PD-1 and PD-L1 inhibitors for solid tumors in our center, during January 2015 and October 2018. A multivariate regression was made to determine potential risk factors for irAE. Significance was stablished at p < 0,05. Statistical analysis was made with STATA.

Results

75 pts were included. Median age as 66 years (28-88y). 47 pts (62%) were male. 67 pts (90%) had metastatic disease. 48 pts (64%) were treated with nivolumab, 17 (22%) with pembrolizumab, 8 (10%) with durvalumab and 2 pts with atezolizumab. The most common diagnosis was non small cell lung cancer, with 53 pts (70%), of which 38 were adenocarcinomas. Urothelial cancer, hepatocellular carcinoma e renal cell cancer had 12%, 6% and 5% of the sample respectively. 31 (42%) pts had irAE. 20 (65%) had grade 2 or lower events, and 5pts had multiple irAE. The most common irAE were endocrine dysfunction, skin toxicity and pneumonitis, with 29%, 25% and 19% respectively. Of the 11 serious irAE (grade 3 or higher), the most common cause was pneumonitis with 5 cases. Median time of occurence was 3 weeks after the first treatment (0-52w). The multivariate regression showed higher likelihood of irAE in patients that were female, odds ratio (OR) of 3,72 (p = 0,037, 95% confidence interval (CI95%) 1,15 - 12,83); Lung adenocarcinoma, OR 3,94 (p = 0,032, CI95% 1,12 - 13,79), history of allergies, OR 17,04 (p = 0,022; CI95%) 1,57 - 191,55); history of autoimmune disease, OR 16,88 (p = 0,002; CI95% 2,75 - 103,48). There was no correlation between drug used, previous thoracic radiotherapy or previous steroid treatment.

Conclusion

This study helped distinguish potential risk factors for irAE, like the female gender and history of allergies. Autoimmune disorders are already reported as risk factores. However the small sample isn't enough for us to draw accurate conclusions. More prospective trials are waranted in this setting.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

中文翻译：

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58P免疫相关不良事件的危险因素：一项回顾性研究

抽象的

背景

具有检查点抑制作用的免疫疗法对于具有整体生存率（OS）的肿瘤治疗已变得越来越重要。然而，这些药物并非无害，并且已经报道了免疫相关的不良事件（irAE）。我们假装评估哪些患者（pts）有发展这些风险的风险。

方法

回顾性评估2015年1月至2018年10月在我们中心接受PD-1和PD-L1抑制剂治疗的所有实体瘤患者的病情。进行多因素回归分析以确定irAE的潜在危险因素。显着性稳定在p <0.05。用STATA进行统计分析。

结果

包括75分。中位年龄为66岁（28-88岁）。男性为47分（62％）。67例（90％）有转移性疾病。尼古鲁单抗治疗48例（64％），派姆单抗治疗17例（22％），杜鲁伐单抗治疗8例（10％），阿妥昔单抗治疗2例。最常见的诊断是非小细胞肺癌，有53分（70％），其中38例是腺癌。尿路上皮癌，肝细胞癌和肾细胞癌分别占样本的12％，6％和5％。31名（42％）患上了irAE。20名（65％）有2级或更低的事件，5分有多次irAE。irAE最常见的是内分泌功能障碍，皮肤毒性和肺炎，分别为29％，25％和19％。在11例严重的irAE（3级或更高）中，最常见的原因是肺炎，其中5例。发生的中位时间是第一次治疗后3周（0-52w）。多元回归分析显示女性患者发生irAE的可能性更高，比值比（OR）为3.72（p = 0,037，95％置信区间（CI95％）为1,15-12,83）；肺腺癌，OR 3,94（p = 0,032，CI95％1,12-13,79），过敏史，OR，17,04（p = 0,022; CI95％）1,57-191,55）; 自身免疫性疾病史，或16,88（p = 0,002; CI95％2,75-103,48）。所用药物，先前的胸腔放疗或先前的类固醇治疗之间没有相关性。

结论

这项研究有助于区分irAE的潜在危险因素，例如女性性别和过敏史。自身免疫性疾病已被报告为危险因素。但是，小样本不足以使我们得出准确的结论。在这种情况下，需要进行更多的前瞻性试验。

负责研究的法人实体

作者。

资金

尚未收到任何资金。

揭露

所有作者均声明没有利益冲突。