Department of Medical Oncology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Cancer Center, Shiga University of Medical Science, Otsu, Shiga, Japan.
PLoS One. 2024 Jul 16;19(7):e0306995. doi: 10.1371/journal.pone.0306995. eCollection 2024.
Immune checkpoint inhibitors (ICIs) have been widely used as standard therapies for various cancers. However, in 20-30% of cases, ICIs can lead to immune-related adverse events (irAEs), which sometimes require discontinuation of treatment. Due to the increased risk of irAEs, patients with pre-existing autoimmune diseases (AI) are often advised against receiving ICIs. However, there has not been sufficient objective risk assessment for AI. In our study, we conducted logistic regression analysis to assess the risk of irAEs by analyzing 478 cases that received anti-PD-(L)1 Ab and/or anti-CTLA4 Ab at our hospital between April 3, 2017, and May 24, 2022. Among these cases, 28 (5.9%) had pre-existing AI. We selected several independent factors for analysis: gender, age, performance status (PS), cancer type, type of ICI, type of combined anti-cancer agents, best overall response, and pre-existing AI. The adjusted odds ratio (OR) of AI for irAE occurrence was 2.52 [95% CI: 1.08-5.86] (p = 0.033), and the adjusted OR of AI for ICI discontinuation due to irAE was 3.32 [1.41-7.78] (p = 0.006). Patients with pre-existing AI experienced a significantly shorter irAE-free survival time compared to those without AI (median irAE-free survival: 5.7 months [95% CI: 3.5-7.8] vs 10.4 months [95% CI: 7.9-12.9], respectively, p = 0.035). Frequently observed irAEs in full ICI cohort, such as dermatologic issues (7.5%), pneumonitis (7.1%), hepatitis (4.6%), and hypothyroidism (4.2%), were often accompanied by pre-existing AI. Furthermore, pre-existing AI flared up in 6 cases (37.5% in AI-positive irAE-positive cases). The activity of AI was not related to the occurrence of irAEs. Grade 3 or higher irAEs were observed in 6 out of 20 (30.0%) cases in AI-accompanied patients complicated with irAEs. Although having a complicated AI increases the risk of irAEs, it may not necessarily be a contraindication for ICI treatment if closely monitored. (292<300 characters).
免疫检查点抑制剂 (ICI) 已被广泛用作各种癌症的标准治疗方法。然而，在 20-30%的情况下，ICI 可导致免疫相关不良事件 (irAE)，有时需要停止治疗。由于 irAE 的风险增加，患有预先存在的自身免疫性疾病 (AI) 的患者通常不建议接受 ICI。然而，对于 AI 并没有进行充分的客观风险评估。在我们的研究中，我们通过分析 2017 年 4 月 3 日至 2022 年 5 月 24 日期间在我院接受抗 PD-(L)1 Ab 和/或抗 CTLA4 Ab 治疗的 478 例病例，进行了逻辑回归分析，以评估 irAE 的风险。在这些病例中，28 例（5.9%）预先存在 AI。我们选择了几个独立因素进行分析：性别、年龄、表现状态 (PS)、癌症类型、ICI 类型、联合抗癌药物类型、最佳总体反应和预先存在的 AI。AI 发生 irAE 的调整后比值比 (OR) 为 2.52[95%CI:1.08-5.86]（p=0.033），AI 因 irAE 而停止 ICI 的调整后 OR 为 3.32[1.41-7.78]（p=0.006）。与没有 AI 的患者相比，预先存在 AI 的患者 irAE 无进展生存期明显更短（中位 irAE 无进展生存期：5.7 个月[95%CI:3.5-7.8] vs 10.4 个月[95%CI:7.9-12.9]，分别，p=0.035）。在全 ICI 队列中经常观察到的 irAE，如皮肤病问题（7.5%）、肺炎（7.1%）、肝炎（4.6%）和甲状腺功能减退症（4.2%），常伴有预先存在的 AI。此外，在 6 例（AI 阳性 irAE 阳性病例的 37.5%）中，预先存在的 AI 出现了恶化。AI 的活动与 irAE 的发生无关。在伴有 irAE 的 AI 患者中，观察到 6 例（30.0%）出现 3 级或更高级别的 irAE。尽管伴有复杂的 AI 会增加 irAE 的风险，但如果密切监测，不一定是 ICI 治疗的禁忌症。（292<300 个字符）
