Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan.
Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
Cancer Immunol Immunother. 2024 Jun 4;73(8):146. doi: 10.1007/s00262-024-03733-2.
Anti-programmed cell death-1 (ligand-1) antibody [PD-(L)1-Ab] can cause destructive thyroiditis and/or hypothyroidism. In addition, tyrosine kinase inhibitors (TKIs) frequently induce hypothyroidism. The aim of this prospective study is to examine the incidence and clinical characteristics of thyroid dysfunction induced by combination therapy of a PD-(L)1-Ab and TKI [PD-(L)1-Ab/TKI].
A total of 757 patients treated with PD-(L)1-Ab or PD-(L)1-Ab/TKI were evaluated for anti-thyroid antibodies (ATAs) at baseline and for thyroid function for 48 weeks after treatment initiation and then observed until the last visit.
The cumulative incidences of destructive thyroiditis [4/23 (17.4%) vs. 45/734 (6.1%) patients, p < 0.001], isolated hypothyroidism [10/23 (43.5%) vs. 29/734 (4.0%) patients, p < 0.001], and all thyroid dysfunction [14/23 (60.9%) vs. 74/734 (10.1%) patients, p < 0.001] were significantly higher in the PD-(L)1-Ab/TKI group than PD-(L)1-Ab group, respectively. All patients positive for ATAs at baseline developed thyroid dysfunction after PD-(L)1-Ab/TKI treatment, a significantly higher incidence than that in those negative for ATAs at baseline [4/4 (100%) vs. 10/19 (52.6%) patients, p = 0.026].
The addition of TKIs increased the risk of thyroid dysfunction induced by PD-(L)1-Ab, with the risk being higher in patients positive for baseline ATAs.
抗程序性死亡-1（配体-1）抗体[PD-(L)1-Ab]可引起破坏性甲状腺炎和/或甲状腺功能减退症。此外，酪氨酸激酶抑制剂（TKI）常引起甲状腺功能减退症。本前瞻性研究的目的是研究 PD-(L)1-Ab 和 TKI[PD-(L)1-Ab/TKI]联合治疗引起的甲状腺功能障碍的发生率和临床特征。
共评估了 757 例接受 PD-(L)1-Ab 或 PD-(L)1-Ab/TKI 治疗的患者，他们在基线时评估抗甲状腺抗体（ATAs），并在治疗开始后 48 周内评估甲状腺功能，然后观察至最后一次就诊。
破坏性甲状腺炎的累积发生率[4/23（17.4%）比 734/734（6.1%）患者，p<0.001]、单纯性甲状腺功能减退症[10/23（43.5%）比 734/734（4.0%）患者，p<0.001]和所有甲状腺功能障碍[14/23（60.9%）比 734/734（10.1%）患者，p<0.001]在 PD-(L)1-Ab/TKI 组明显高于 PD-(L)1-Ab 组。所有基线时 ATAs 阳性的患者在接受 PD-(L)1-Ab/TKI 治疗后均发生甲状腺功能障碍，发生率明显高于基线时 ATAs 阴性的患者[4/4（100%）比 19/19（52.6%）患者，p=0.026]。
TKI 的加入增加了 PD-(L)1-Ab 引起的甲状腺功能障碍的风险，基线时 ATAs 阳性的患者风险更高。
