A real-world study on the safety of the extended dosing schedule for nivolumab and pembrolizumab in patients with solid tumors
A real-world study on the safety of the extended dosing schedule for nivolumab and pembrolizumab in patients with solid tumors
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DOI：
10.1016/j.intimp.2022.108775
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发表时间：
2022-04-15
影响因子：
5.6
通讯作者：
Takayama, Koichi
中科院分区：
文献类型：
--
作者：
Morimoto, Kenji;Yamada, Tadaaki;Takayama, Koichi
背景资料：除了2周一次的nivolumab 240 mg或3周一次的pembrolizumab 200 mg外，还批准了4周一次的nivolumab 480 mg或6周一次的pembrolizumab 200 mg的延长给药间隔。迄今为止，尚未在实体瘤患者中充分研究免疫检查点抑制剂（ICI）延长给药方案的临床安全性。研究方法：这项真实世界研究招募了2020年8月至2021年12月期间在日本京都县立医科大学接受nivolumab 480 mg每4周一次或pembrolizumab 400 mg每6周一次治疗的实体瘤患者。结果：69例实体瘤患者在此期间接受了延长间隔给药方案。其中，60人在治疗期间接受了治疗（队列A），9人首次接受治疗（队列B）。在队列A中延长ICI给药间隔后，13例（21.7%）患者发生免疫相关不良事件（irAE）。13例患者中有7例（53.8%）在延长给药间隔的第一个周期内发生irAE。在延长给药间隔的第一个周期内发生irAE的所有患者均存在既存抗体。多变量分析表明，在开始延长给药间隔后，既存抗甲状腺抗体的患者的irAE发生率显著更高（比值比：6.41; 95%置信区间：1.46-28.2，p = 0.01）。结论：大多数患者在延长给药间隔后被允许继续ICI治疗。既存抗体（尤其是抗甲状腺抗体）患者在开始延长给药间隔后可能易于发生irAE，应谨慎治疗。
Background: In addition to 2-weekly nivolumab 240 mg or 3-weekly pembrolizumab 200 mg, extended dosing intervals of 4-weekly nivolumab 480 mg or 6-weekly pembrolizumab 200 mg were approved. To date, the clinical safety of the extended dosing schedules of immune checkpoint inhibitors (ICIs) has not been adequately investigated in patients with solid tumors. Methods: This real-world study enrolled patients with solid tumors who received nivolumab 480 mg every 4 weeks or pembrolizumab 400 mg every 6 weeks at the Kyoto Prefectural University of Medicine in Japan, between August 2020 and December 2021. Results: Sixty-nine patients with solid tumors received an extended-interval dosing schedule during this period. Among them, 60 received it during treatment (cohort A), and nine received it for the first time (cohort B). After the extended dosing interval of ICIs in cohort A, 13 (21.7%) patients developed immune-related adverse events (irAEs). Seven of the 13 patients (53.8%) developed irAEs during the first cycle of the extended dosing interval. All patients who developed irAEs during the first cycle of the extended dosing interval had pre-existing antibodies. Multivariate analysis indicated that patients with pre-existing anti-thyroid antibodies had a significantly higher irAE incidence after starting extended dosing intervals (odds ratio: 6.41; 95% confidence interval: 1.46-28.2, p = 0.01). Conclusions: Most patients were allowed to continue ICI therapy after an extended dosing interval. Patients with pre-existing antibodies, particularly anti-thyroid antibodies, may be prone to developing irAEs after starting extended dosing intervals and should be treated with caution.