Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of VIP Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Hum Vaccin Immunother. 2024 Dec 31;20(1):2410557. doi: 10.1080/21645515.2024.2410557. Epub 2024 Oct 8.
This study utilized meta-analysis and Mendelian randomization (MR) to identify risk factors for endocrine-related immune-related adverse events (EirAEs) and to ascertain whether EirAEs confer better prognosis of immunotherapy. The meta-analysis identified several risk factors for EirAEs, including elevated baseline TSH (OR = 1.30, 95% CI 1.10-1.53), positive TgAb (OR = 14.23, < .001), positive TPOAb (OR = 3.75, < .001), prior thyroid-related medical history (OR = 4.19), increased BMI (OR = 1.11), combination immune checkpoint inhibitors (ICIs) therapy with targeted treatment (OR = 2.71, 95% CI 2.11-3.47), and dual ICI therapy (OR = 3.26, 95% CI 2.22-4.79). MR analysis further supported causalities between extreme BMI, hypothyroidism, and irAEs from a genetic perspective. In addition, cancer patients who experienced EirAEs exhibited significantly prolonged PFS (HR = 0.84, 95% CI 0.73-0.97) and OS (HR = 0.59, 95% CI 0.45-0.76) compared to those without. These findings provide valuable insights for clinical decision-making among healthcare professionals and offer direction for future research in this field.
本研究采用荟萃分析和孟德尔随机化（MR）来确定内分泌相关免疫相关不良事件（EirAEs）的风险因素，并确定 EirAEs 是否能改善免疫治疗的预后。荟萃分析确定了几个 EirAEs 的风险因素，包括基线 TSH 升高（OR=1.30，95%CI 1.10-1.53）、TgAb 阳性（OR=14.23， <.001）、TPOAb 阳性（OR=3.75， <.001）、甲状腺相关既往病史（OR=4.19）、BMI 增加（OR=1.11）、联合免疫检查点抑制剂（ICIs）与靶向治疗（OR=2.71，95%CI 2.11-3.47）、双重 ICI 治疗（OR=3.26，95%CI 2.22-4.79）。MR 分析进一步从遗传角度支持了极端 BMI、甲状腺功能减退和 irAEs 之间的因果关系。此外，发生 EirAEs 的癌症患者的 PFS（HR=0.84，95%CI 0.73-0.97）和 OS（HR=0.59，95%CI 0.45-0.76）明显长于未发生 EirAEs 的患者。这些发现为临床医生提供了有价值的决策参考，并为该领域的未来研究提供了方向。
