Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Int Immunopharmacol. 2022 Jul;108:108775. doi: 10.1016/j.intimp.2022.108775. Epub 2022 Apr 15.
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.
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.
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).
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.
除了每 2 周给予 240mg 纳武利尤单抗或每 3 周给予 200mg 帕博利珠单抗外，还批准了每 4 周给予 480mg 纳武利尤单抗或每 6 周给予 200mg 帕博利珠单抗的延长给药间隔。迄今为止，免疫检查点抑制剂（ICI）的延长给药方案在实体瘤患者中的临床安全性尚未得到充分研究。
本真实世界研究纳入了 2020 年 8 月至 2021 年 12 月期间在日本京都府立医科大学接受每 4 周给予 480mg 纳武利尤单抗或每 6 周给予 400mg 帕博利珠单抗治疗的实体瘤患者。
在此期间，69 例实体瘤患者接受了延长间隔给药方案。其中，60 例在治疗期间接受（队列 A），9 例首次接受（队列 B）。在队列 A 中开始 ICI 的延长间隔给药后，13（21.7%）例患者发生免疫相关不良事件（irAE）。在延长间隔给药的第一个周期中，13 例患者中的 7 例（53.8%）发生 irAE。在延长间隔给药的第一个周期中发生 irAE 的所有患者均存在预先存在的抗体。多变量分析表明，开始延长间隔给药后，存在预先存在的甲状腺抗体的患者 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）。
大多数患者在延长给药间隔后仍可继续接受 ICI 治疗。存在预先存在的抗体，特别是甲状腺抗体的患者，在开始延长间隔给药后可能更容易发生 irAE，应谨慎治疗。
