Takada Hitomi, Yamashita Koji, Osawa Leona, Komiyama Yasuyuki, Muraoka Masaru, Suzuki Yuichiro, Sato Mitsuaki, Kobayashi Shoji, Yoshida Takashi, Takano Shinichi, Maekawa Shinya, Enomoto Nobuyuki
Gastroenterology and Hepatology Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Hepatol Res. 2024 Feb;54(2):162-173. doi: 10.1111/hepr.13969. Epub 2023 Oct 6.
Atezolizumab plus bevacizumab (AB) combination therapy is the first-line treatment for unresectable hepatocellular carcinoma (u-HCC). The management of immune-related adverse events (irAEs) is an important issue associated with achieving a good therapeutic response in patients receiving AB therapy. However, few studies have reported irAE development in patients receiving AB therapy. This study focused on the association between irAE development and autoantibodies at baseline in patients receiving AB therapy.
Sixty-one patients receiving AB therapy were enrolled. For autoantibodies, the following antibodies were tested before the start of AB therapy: antinuclear antibodies, rheumatoid factor (RF), anti-thyroglobulin antibodies, thyroid peroxidase antibodies, anti-thyroid stimulating hormone receptor antibodies, and acetylcholine receptor antibodies. A patient was considered to have pre-existing antibodies if any of the listed antibodies were present at baseline.
Ten patients (16%) developed irAEs during the observation period. The irAEs included liver injury, hypothyroidism, adrenal insufficiency, adrenocorticotropic hormone deficiency, and rhabdomyolysis. Patients with irAE (n = 10) were more likely to be positive for any autoantibody (hazard ratio [HR] 3.7, p = 0.047) and RF at baseline (HR 5.4, p = 0.035) and to achieve complete response (HR 5.8, p = 0.027) than those without. The presence of autoantibodies at baseline was an independent factor associated with irAE development.
In the real world, 16% of patients receiving AB therapy for u-HCC developed irAEs. Patients with autoantibodies at baseline are at high risk of developing irAEs and require cautious follow-up.
阿替利珠单抗联合贝伐单抗(AB)联合疗法是不可切除肝细胞癌(u-HCC)的一线治疗方案。免疫相关不良事件(irAE)的管理是接受AB治疗的患者获得良好治疗反应的一个重要问题。然而,很少有研究报道接受AB治疗的患者发生irAE的情况。本研究聚焦于接受AB治疗的患者基线时irAE发生与自身抗体之间的关联。
纳入61例接受AB治疗的患者。对于自身抗体,在AB治疗开始前检测以下抗体:抗核抗体、类风湿因子(RF)、抗甲状腺球蛋白抗体、甲状腺过氧化物酶抗体、抗促甲状腺激素受体抗体和乙酰胆碱受体抗体。如果基线时存在任何一种所列抗体,则认为该患者存在预先存在的抗体。
10例患者(16%)在观察期内发生irAE。irAE包括肝损伤、甲状腺功能减退、肾上腺功能不全、促肾上腺皮质激素缺乏和横纹肌溶解。发生irAE的患者(n = 10)在基线时更有可能任何自身抗体呈阳性(风险比[HR] 3.7,p = 0.047)和RF呈阳性(HR 5.4,p = 0.035),并且比未发生irAE的患者更有可能实现完全缓解(HR 5.8,p = 0.027)。基线时自身抗体的存在是与irAE发生相关的独立因素。
在现实世界中,16%接受AB治疗的u-HCC患者发生了irAE。基线时存在自身抗体的患者发生irAE的风险较高,需要谨慎随访。