Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Department of Gastroenterology, Hepatology and Nutrition, Unit 1466, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
J Cancer Res Clin Oncol. 2023 Aug;149(9):6341-6350. doi: 10.1007/s00432-023-04582-9. Epub 2023 Feb 8.
Immune checkpoint inhibitor (ICI) therapy can predispose patients to immune-related adverse events (irAEs) and autoimmune disease (AD) flare-ups, but the characteristics of irAEs among patients with pre-existing ADs are largely unknown. We conducted this study to determine the clinical courses, irAEs, AD flares, treatment, and outcomes of patients with AD on ICIs.
This was a retrospective study of adult cancer patients at a large cancer center who were diagnosed with ADs before undergoing ICI therapy. Patients' clinical courses, complications, treatments, and outcomes related to both ADs flares and irAEs were collected and analyzed.
The study included 197 patients. Most (55.4%) were women. Melanoma comprised the highest proportion (28.4%) of malignancies, and most (83.8%) patients received PD-1/PD-L1 inhibitors. Fifty (25.3%) patients developed a new irAE after starting ICI therapy, while 29 (14.7%) patients had an AD flare-up. Patients with inflammatory bowel disease had the highest incidence of AD flare-ups (31.7%), while patients with Hashimoto hypothyroidism had the highest incidence of new irAEs (39.2%). Patients with inflammatory bowel disease had more severe adverse events. In our cohort, patients with a new diagnosis of irAE were treated with immunosuppressive therapy. AD flares were managed similarly. With regard to irAE manifestations, the most common presentations were colitis (24 [12.1%] patients), hepatic transaminase elevations (8 [4%] patients), and pneumonitis (7 [3.5%] patients).
Our findings suggest that patients with gastrointestinal and rheumatologic ADs had a higher incidence of AD flare-ups, while patients with Hashimoto hypothyroidism and neurologic ADs had a higher incidence of new irAEs. Patients with prior ADs experiencing flare-ups or new irAEs after ICI therapy tend to require aggressive immunosuppressive treatment. Thorough evaluation of baseline disease status, appropriate medical management before ICI therapy, and early recognition of inflammatory exacerbation may help ensure long-term success in treating and improving outcomes in these patients.
免疫检查点抑制剂(ICI)治疗可使患者易发生免疫相关不良事件(irAE)和自身免疫性疾病(AD)发作,但先前存在 AD 的患者的 irAE 特征在很大程度上尚不清楚。我们进行这项研究旨在确定接受 ICI 治疗的患有 AD 的患者的临床过程、irAE、AD 发作、治疗和结局。
这是一项回顾性研究,纳入了在一家大型癌症中心接受 ICI 治疗前被诊断为 AD 的成年癌症患者。收集并分析了与 AD 发作和 irAE 相关的患者的临床过程、并发症、治疗和结局。
该研究纳入了 197 例患者。大多数(55.4%)为女性。黑素瘤占恶性肿瘤的比例最高(28.4%),大多数(83.8%)患者接受了 PD-1/PD-L1 抑制剂治疗。50 例(25.3%)患者在开始 ICI 治疗后出现新的 irAE,29 例(14.7%)患者出现 AD 发作。患有炎症性肠病的患者 AD 发作的发生率最高(31.7%),而患有桥本甲状腺功能减退症的患者新发生 irAE 的发生率最高(39.2%)。患有炎症性肠病的患者发生更严重的不良事件。在本队列中,新发 irAE 的患者接受了免疫抑制治疗。AD 发作的治疗方法类似。就 irAE 表现而言,最常见的表现为结肠炎(24 例[12.1%]患者)、肝转氨酶升高(8 例[4%]患者)和肺炎(7 例[3.5%]患者)。
我们的研究结果表明,胃肠道和风湿性 AD 患者的 AD 发作发生率较高,而桥本甲状腺功能减退症和神经 AD 患者的新发生 irAE 发生率较高。在接受 ICI 治疗后出现 AD 发作或新发生 irAE 的先前存在 AD 的患者往往需要积极的免疫抑制治疗。在接受 ICI 治疗之前,对基础疾病状态进行全面评估、适当的医疗管理以及早期识别炎症加重,可能有助于确保这些患者的治疗长期成功并改善结局。