Sintilimab-Induced Autoimmune Diabetes in a Patient With the Anti-tumor Effect of Partial Regression
Sintilimab-Induced Autoimmune Diabetes in a Patient With the Anti-tumor Effect of Partial Regression
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信迪利单抗诱导的自身免疫性糖尿病患者的抗肿瘤作用部分回归
DOI：
10.3389/fimmu.2020.02076
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发表时间：
2020-08-21
影响因子：
7.3
通讯作者：
Liang, Tingbo
中科院分区：
文献类型：
--
作者：
Wen, Liang;Zou, Xiuwen;Liang, Tingbo
免疫检查点阻断（ICBs）已被广泛批准用于治疗各种恶性肿瘤。可由程序性细胞死亡蛋白1（PD-1）抑制剂引起的自身免疫性糖尿病是罕见的。Sintilimab是一种单克隆抗PD-1抗体，已在中国获批用于治疗霍奇金淋巴瘤，并在我们的临床试验中用于不可切除的肝细胞癌（HCC）患者。病例介绍我们介绍了第一例在Sintiliumab治疗不可切除的HCC患者期间发生自身免疫性糖尿病的病例，伴随着部分消退的显着抗肿瘤作用。一名具有典型症状的56岁男性在Sintilimab开始治疗后24周出现糖尿病酮症酸中毒（DKA）。他的空腹血糖水平为22.2 mmol/L，HbA 1c为7.8%，空腹胰岛素为1.5 mIU/L，空腹C肽为1.12 ng/mL，4天后进一步降至0.21 ng/mL。通过口服葡萄糖耐量试验，患者被诊断为新发糖尿病。抗谷氨酸脱羧酶65抗体、抗胰岛细胞抗体和抗胰岛素抗体试验均为阴性。对于人类白细胞抗原（HLA）I类和II类的1型糖尿病相关等位基因，最相关的类型被鉴定为HLA-A β 0201。诊断为PD-1通路诱导的自身免疫性糖尿病。DKA纠正后，他每天接受胰岛素治疗，此后血糖控制良好。此后，继续使用Sintilimab，持续治疗效果。结论由于该罕见的免疫相关不良事件（irAE）的不可预测性，建议在免疫治疗前检测糖尿病相关自身抗体和C肽，并进行血糖监测。在使用胰岛素治疗良好控制血糖后，PD-1抑制剂治疗可能会继续，特别是当免疫治疗有效时。
Context Immune checkpoint blockades (ICBs) have been approved widely to treat various malignancies. Autoimmune diabetes mellitus, which can be caused by programmed cell death protein 1 (PD-1) inhibitors, is rare. Sintilimab, a monoclonal anti-PD-1 antibody, has been approved in China for the treatment of Hodgkin’s lymphoma and was used in our clinical trial for patients with unresectable hepatocellular carcinoma (HCC). Case Presentation We present the first case of autoimmune diabetes during Sintilimab treatment in a patient with unresectable HCC, accompanied by a remarkable anti-tumor effect of partial regression. A 56-year-old male with typical symptoms presented with diabetic ketoacidosis (DKA) at 24 weeks after Sintilimab initiation. His fasting plasma glucose level was 22.2 mmol/L, HbA1c was 7.8%, fasting insulin was 1.5 mIU/L, and fasting C-peptide was 1.12 ng/mL, which further decreased to 0.21 ng/mL 4 days later. The patient was diagnosed with new-onset diabetes mellitus using the oral glucose tolerance test. The anti-glutamic acid decarboxylase 65 antibody, anti-islet cell antibody, and anti-insulin antibody tests were all negative. For the type 1 diabetes-associated alleles of human leukocyte antigen (HLA) class I and II, the most relevant type was identified as HLA-A∗0201. A diagnosis of PD-1 inhibitor-induced autoimmune diabetes was made. After rectification of DKA, he was treated with insulin therapy daily, which has since controlled his plasma glucose well. Thereafter, Sintilimab was been continued with sustained therapeutic effect. Conclusion Due to unpredictability of this rare immune related adverse event (irAE), diabetes-related autoantibodies and C-peptide are recommended to be tested before immunotherapy, and plasma glucose monitoring should be performed. After plasma glucose is well controlled using insulin therapy, PD-1 inhibitor treatment might be continued, especially when the immunotherapy is effective.