Department of Medicine, University of Chicago Medical Center, Chicago, IL, USA.
Department of Medicine, Section of Hematology Oncology, Chicago, IL, USA.
Oncologist. 2023 May 8;28(5):440-448. doi: 10.1093/oncolo/oyac252.
Side effects of immune checkpoint inhibitors (ICIs), called immune-related adverse events (irAEs), closely resemble primary autoimmune or rheumatic diseases. We aimed to understand the clinical utility of rheumatic autoantibodies (rhAbs) for diagnosing irAEs.
Patients without pre-existing autoimmune disease (pAID) who had cancer treated with ICI(s) treatment from 1/1/2011 to 12/21/2020 and a rhAb checked were retrospectively identified. Logistic regression assessed associations between autoantibodies and irAEs, cancer outcome, and survival. Specificity, sensitivity, and positive/negative predictive values (PPV, NPV) were estimated for key rhAbs and ICI-arthritis. Kaplan-Meier analyzed objective response rate (ORR) and overall survival (OS).
A total of 2662 patients were treated with≥1 ICIs. One hundred and thirty-five without pAID had ≥ 1 rhAb tested. Of which 70/135(52%) were female; median age at cancer diagnosis was 62 years with most common cancers: melanoma (23%) or non-small cell lung cancer (21%), 96/135 (75%) were anti-PD1/PDL1 treated. Eighty had a rhAb ordered before ICI, 96 after ICI, and 12 before and after. Eighty-two (61%) experienced an irAE, 33 (24%) with rheumatic-irAE. Pre-ICI RF showed significant association with rheumatic-irAEs (OR = 25, 95% CI, 1.52-410.86, P = .024). Pre- and post-ICI RF yielded high specificity for ICI-arthritis (93% and 78%), as did pre- and post-ICI CCP (100% and 91%). Pre-ICI RF carried 93% NPV and pre-ICI CCP had 89% PPV for ICI-arthritis. No variables were significantly correlated with ORR. Any-type irAE, rheumatic-irAE and ICI-arthritis were all associated with better OS (P = .000, P = .028, P = .019).
Pre-ICI RF was associated with higher odds of rheumatic-irAEs. IrAEs had better OS; therefore, clinical contextualization for rhAbs is critical to prevent unnecessary withholding of lifesaving ICI for fear of irAEs.
免疫检查点抑制剂（ICIs）的副作用，称为免疫相关不良事件（irAEs），与原发性自身免疫或风湿性疾病非常相似。我们旨在了解风湿自身抗体（rhAbs）在诊断 irAEs 中的临床应用。
回顾性分析了 2011 年 1 月 1 日至 2020 年 12 月 21 日期间接受 ICI（s）治疗且无自身免疫疾病（pAID）的癌症患者，并对其进行了 rhAb 检测。逻辑回归评估了自身抗体与 irAEs、癌症结局和生存之间的关系。估计了关键 rhAbs 和 ICI 关节炎的特异性、敏感性和阳性/阴性预测值（PPV、NPV）。Kaplan-Meier 分析了客观缓解率（ORR）和总生存期（OS）。
共 2662 例患者接受了≥1 种 ICIs 治疗。135 例无 pAID 患者检测了≥1 种 rhAb。其中 70/135（52%）为女性；癌症诊断时的中位年龄为 62 岁，最常见的癌症为黑色素瘤（23%）或非小细胞肺癌（21%），96/135（75%）接受了抗 PD1/PDL1 治疗。80 例在 ICI 前、96 例在 ICI 后、12 例在 ICI 前后进行了 rhAb 检测。82 例（61%）发生了 irAE，其中 33 例（24%）为风湿性 irAE。ICI 前 RF 与风湿性 irAEs 有显著相关性（OR=25，95%CI，1.52-410.86，P=0.024）。ICI 前和后 RF 对 ICI 关节炎均具有较高的特异性（93%和 78%），ICI 前和后 CCP 也具有较高的特异性（100%和 91%）。ICI 前 RF 对 ICI 关节炎的阴性预测值为 93%，ICI 前 CCP 的阳性预测值为 89%。没有变量与 ORR 显著相关。任何类型的 irAE、风湿性 irAE 和 ICI 关节炎均与更好的 OS 相关（P=0.000，P=0.028，P=0.019）。
ICI 前 RF 与风湿性 irAEs 的发生几率更高相关。irAEs 具有更好的 OS；因此，对 rhAbs 进行临床背景分析对于防止因担心 irAEs 而不必要地拒绝救命的 ICI 至关重要。
