Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade
Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade
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DOI：
10.1210/clinem/dgac467
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发表时间：
2022-08-03
影响因子：
5.8
通讯作者：
Arima, Hiroshi
中科院分区：
文献类型：
--
作者：
Kobayashi, Tomoko;Iwama, Shintaro;Arima, Hiroshi
背景：甲状腺功能障碍通常是由抗程序性细胞死亡-1配体1抗体(PD-L1-Abs)和抗癌药物引起的，包括Ramucirumab(RAM)和多靶点酪氨酸激酶抑制剂(MULTI-TKI)，这两种药物通常在PD-L1-Ab治疗癌症患者之前使用。方法148例接受PD-L1-Abs治疗的患者在治疗开始后24周内每隔6周检测一次抗甲状腺抗体和甲状腺功能，并观察至治疗结束。结果148例患者中，15例(10.1%)在PD-L1-Ab治疗后出现甲状腺功能障碍，其中破坏性甲状腺炎8例，甲状腺功能减退症7例。在有甲状腺功能障碍的患者中，基线时促甲状腺激素(TSH)水平升高(3/15[20.0%]vs 4/133[3.0%]，P<；0.05)、抗甲状腺球蛋白抗体(TgAbs)阳性(4/15[26.7%]vs 5/133[3.8%]，P<；0.05)和既往接受RAM或多TKI治疗的患者(3/15[20.0%]vs 5/133[3.8%]，P<；0.05)显著高于无甲状腺功能障碍的患者。在多因素分析中，基线TSH值升高、TgAb阳性、接受随机对照或多TKI治疗与甲状腺功能障碍的发生显著相关，OR值分别为7.098(95%可信区间1.154~43.638)、11.927(95%可信区间2.526~56.316)和8.476(95%可信区间1.592~45.115)。结论本研究结果提示PD-L1-Abs引起甲状腺功能障碍的风险可以通过基线TSH水平、TgAb阳性和接受RAM或多个TKI治疗来预测。
Background Thyroid dysfunction is frequently caused by treatment with antiprogrammed cell death-1 ligand 1 antibodies (PD-L1-Abs) and anticancer drugs, including ramucirumab (RAM) and multitargeted tyrosine kinase inhibitors (multi-TKIs), which are often used prior to PD-L1-Ab treatment in cancer patients. Methods A total of 148 patients treated with PD-L1-Abs were evaluated for antithyroid antibodies at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then were observed until the visits stopped. Results Of the 148 patients, 15 (10.1%) developed thyroid dysfunction after PD-L1-Ab treatment (destructive thyroiditis in 8 and hypothyroidism without preceding thyrotoxicosis in 7). The prevalence of an elevated thyroid-stimulating hormone (TSH) level at baseline (3/15 [20.0%] vs 4/133 [3.0%], P < .05), positive antithyroglobulin antibodies (TgAbs) at baseline (4/15 [26.7%] vs 5/133 [3.8%], P < .05) and prior treatment with RAM or multi-TKIs (3/15 [20.0%] vs 5/133 [3.8%], P < .05) were significantly higher in patients with vs without thyroid dysfunction. In a multivariate analysis, elevated TSH level at baseline, TgAb positivity at baseline, and prior treatment with RAM or multi-TKIs were significantly associated with the development of thyroid dysfunction, with ORs of 7.098 (95% CI 1.154-43.638), 11.927 (95% CI 2.526-56.316), and 8.476 (95% CI 1.592-45.115), respectively. Conclusion The results of this real-world study suggest that the risk of thyroid dysfunction induced by PD-L1-Abs can be predicted by the TSH level at baseline, TgAb positivity at baseline, and prior treatment with RAM or multi-TKIs.