Division of Hematology/Oncology, Department of Medicine, Tufts Medical Center, Boston, MA, USA.
School of Medicine, Tufts Medical Center, Boston, MA, USA.
Eur J Haematol. 2021 Dec;107(6):650-657. doi: 10.1111/ejh.13703. Epub 2021 Sep 3.
With the increased use of immune checkpoint inhibitors (ICI), it is essential to improve our understanding of immune-related adverse events (irAE). To date, most studies describing irAE have been performed in clinical trial populations, which may not be an accurate description of irAE in real-world populations. Also, identification of patients at increased risk of irAE is needed as early recognition may improve irAE outcomes.
We performed a retrospective analysis of patients who received an ICI between January 2014 and October 2018 at a single institution (Tufts Medical Center). Each patient was followed for up to 12 months for the outcome of a physician-reported irAE. Kaplan-Meier curves were created for the time to development and resolution of initial irAE. A Cox proportional hazards model was created to evaluate whether the following variables were independent predictors of an initial irAE: age ≥65 years, female sex, non-Caucasian race, radiation in previous 6 months, current smoking status, melanoma, and combination ICI (ipilimumab and nivolumab).
Of 131 patients followed, 57 patients (43.5%) developed at least one irAE at a median of 250 days (95% confidence interval (CI) 132 days-not estimable). The most common irAE included dermatitis, thyroid dysfunction, and pneumonitis. Nearly two-thirds of patients with an irAE had ICI therapy withdrawn, and nearly 60% had immunosuppression initiated. In multivariable analysis, we found a significant association between irAE development and age ≥65 years hazard ratio (HR) 1.80, 95% CI (1.03-3.14) and current smoking status (HR 2.26, 95% CI 1.06-4.82).
We detected a high rate of irAE and that irAE and subsequent management can be clinically burdensome in this patient population. While further studies are needed to validate these findings, this study provides insights into the magnitude, time course, management of, and possible predictors of irAE in a real-world setting.
随着免疫检查点抑制剂（ICI）的应用增加，提高我们对免疫相关不良事件（irAE）的认识至关重要。迄今为止，大多数描述 irAE 的研究都是在临床试验人群中进行的，这可能无法准确描述真实人群中的 irAE。此外，还需要确定发生 irAE 风险增加的患者，因为早期识别可能会改善 irAE 结局。
我们对 2014 年 1 月至 2018 年 10 月在一家机构（塔夫茨医疗中心）接受 ICI 治疗的患者进行了回顾性分析。每位患者在 12 个月内接受随访，以了解医生报告的 irAE 的结局。为初始 irAE 的发生和缓解时间绘制 Kaplan-Meier 曲线。创建 Cox 比例风险模型来评估以下变量是否为初始 irAE 的独立预测因素：年龄≥65 岁、女性、非白种人、6 个月内接受过放疗、当前吸烟状态、黑色素瘤和联合 ICI（ipilimumab 和 nivolumab）。
在 131 例随访患者中，57 例（43.5%）在中位时间 250 天（95%置信区间（CI）132 天-不可估计）时发生了至少一次 irAE。最常见的 irAE 包括皮炎、甲状腺功能障碍和肺炎。近三分之二有 irAE 的患者停止了 ICI 治疗，近 60%的患者开始接受免疫抑制治疗。多变量分析发现，irAE 发生与年龄≥65 岁（风险比（HR）1.80，95%CI（1.03-3.14））和当前吸烟状态（HR 2.26，95%CI 1.06-4.82）显著相关。
我们发现该患者人群中 irAE 发生率较高，irAE 及其后续管理可能会给临床带来负担。虽然还需要进一步研究来验证这些发现，但本研究提供了对真实环境中 irAE 的严重程度、时间进程、管理和可能的预测因素的深入了解。
