Risk factors for immune-related adverse events associated with anti-PD-1 pembrolizumab
Risk factors for immune-related adverse events associated with anti-PD-1 pembrolizumab
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DOI：
10.1038/s41598-019-50574-6
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发表时间：
2019-10-01
影响因子：
4.6
通讯作者：
Lee, Jaejoon
中科院分区：
文献类型：
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作者：
Eun, Yeonghee;Kim, In Young;Lee, Jaejoon
我们调查了接受抗程序性细胞死亡蛋白 1 抗体派姆单抗治疗的患者中免疫相关不良事件 (irAE) 的危险因素。对 2015 年 6 月至 2017 年 12 月期间在韩国首尔三星医疗中心接受至少一剂派姆单抗的所有患者进行了回顾性病历审查。该研究纳入了 391 名患者。收集有关基线特征、治疗细节和不良事件的数据。使用单变量和多变量逻辑回归模型来识别 irAE 的危险因素。 67 名 (17.1%) 患者经历了临床上显着的 irAE；最常见的是皮肤病，其次是肺炎、肌肉骨骼疾病和内分泌疾病。 14 名患者 (3.6%) 经历了严重的 irAE（等级 >= 3）。最常见的严重 irAE 是肺炎（2.3%）。 4 例死亡与 irAE 相关，所有死亡均由肺炎引起。在多变量回归分析中，较高的体重指数 (BMI) 和派姆单抗的多个周期与较高的 irAE 风险相关（BMI：比值比 [OR] 1.08，95% 置信区间 [CI] 1.01-1.16；派姆单抗周期：OR 1.15，95% CI 1.08-1.22）。基线时衍生的中性粒细胞-淋巴细胞比率 (dNLR) 大于 3 与 irAE 风险较低相关（OR 0.37，95% CI 0.17-0.81）。我们的研究表明，BMI 升高和派姆单抗治疗周期数增多与接受派姆单抗治疗的患者发生 irAE 的风险增加相关。此外，基线时 dNLR 的增加与发生 irAE 的风险呈负相关。
We investigated risk factors for immune-related adverse events (irAEs) in patients treated with anti-programmed cell death protein1 antibody pembrolizumab. A retrospective medical record review was performed to identify all patients who received at least one dose of pembrolizumab at Samsung Medical Center, Seoul, Korea between June 2015 and December 2017. Three hundred and ninety-one patients were included in the study. Data were collected on baseline characteristics, treatment details, and adverse events. Univariate and multivariate logistic regression models were used to identify risk factors for irAEs. Sixty-seven (17.1%) patients experienced clinically significant irAEs; most commonly dermatologic disorders, followed by pneumonitis, musculoskeletal disorders, and endocrine disorders. Fourteen patients (3.6%) experienced serious irAEs (grade >= 3). Most common serious irAEs were pneumonitis (2.3%). Four deaths were associated with irAEs, all of which were due to pneumonitis. In multivariate regression analysis, a higher body mass index (BMI) and multiple cycles of pembrolizumab were associated with higher risk of irAEs (BMI: odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01-1.16; pembrolizumab cycle: OR 1.15, 95% CI 1.08-1.22). A derived neutrophil-lymphocyte ratio (dNLR) greater than 3 at baseline was correlated with low risk of irAEs (OR 0.37, 95% CI 0.17-0.81). Our study demonstrated that an elevated BMI and higher number of cycles of pembrolizumab were associated with an increased risk of irAEs in patients treated with pembrolizumab. Additionally, increased dNLR at baseline was negatively correlated with the risk of developing irAEs.