PDF(Pubmed)
Abstract：
Durvalumab is an immune checkpoint Inhibitor (ICIs) that is used in the treatment of malignant tumors, such as lung cancer and melanoma. ICIs are associated with immune-related adverse events including autoimmune encephalitis, although both paraneoplastic phenomena and ICI treatment may lead to autoimmunity.
We describe a 72-year old male patient with small-cell lung cancer, who during adjuvant treatment with Durvalumab developed GABABR1 and GAD65 antibodies and both diabetes and autoimmune limbic encephalitis. Because he was followed prospectively as part of a treatment study, we had access to repeated serum samples and cognitive assessments over time prior to developing encephalitis and diabetes, in addition to later assessments. A high titer of GABABR1 antibodies appeared early, while GAD65 antibodies appeared later with a lower titer in parallel with the development of diabetes. As he subsequently developed clinical signs of encephalitis, verified by EEG and brain MRI, he also had CSF GABABR1 antibodies. Durvalumab was discontinued and steroid treatment with subsequent plasmapheresis were started, resulting in reduction of both CSF and serum antibody levels. Clinical signs of encephalitis gradually improved.
This case illustrates the importance of being aware of possible serious autoimmune adverse reactions, including neurological syndromes such as encephalitis, when treating patients with high risk of para-neoplasia with ICIs. In addition, the case shows the development of autoantibodies over time.
We describe a 72-year old male patient with small-cell lung cancer, who during adjuvant treatment with Durvalumab developed GABABR1 and GAD65 antibodies and both diabetes and autoimmune limbic encephalitis. Because he was followed prospectively as part of a treatment study, we had access to repeated serum samples and cognitive assessments over time prior to developing encephalitis and diabetes, in addition to later assessments. A high titer of GABABR1 antibodies appeared early, while GAD65 antibodies appeared later with a lower titer in parallel with the development of diabetes. As he subsequently developed clinical signs of encephalitis, verified by EEG and brain MRI, he also had CSF GABABR1 antibodies. Durvalumab was discontinued and steroid treatment with subsequent plasmapheresis were started, resulting in reduction of both CSF and serum antibody levels. Clinical signs of encephalitis gradually improved.
This case illustrates the importance of being aware of possible serious autoimmune adverse reactions, including neurological syndromes such as encephalitis, when treating patients with high risk of para-neoplasia with ICIs. In addition, the case shows the development of autoantibodies over time.
摘要：
■Durvalumab是一种免疫检查点抑制剂（ICIs），用于治疗恶性肿瘤，如肺癌和黑色素瘤。ICI与免疫相关的不良事件相关，包括自身免疫性脑炎，尽管副肿瘤现象和ICI治疗都可能导致自身免疫。
■我们描述了一位72岁的男性小细胞肺癌患者，在Durvalumab辅助治疗期间,患者出现了GABABR1和GAD65抗体,同时出现了糖尿病和自身免疫性边缘叶脑炎.因为作为治疗研究的一部分，他被前瞻性地追踪，在发展为脑炎和糖尿病之前，随着时间的推移，我们可以获得重复的血清样本和认知评估，除了以后的评估。高滴度的GABABR1抗体出现早期，而GAD65抗体出现较晚，滴度较低，与糖尿病的发展平行。当他随后出现脑炎的临床症状时，通过脑电图和脑部MRI证实，他也有CSFGABABABR1抗体.停用Durvalumab，并开始随后血浆置换的类固醇治疗，导致CSF和血清抗体水平降低。脑炎的临床体征逐渐好转。
■此案例说明了意识到可能的严重自身免疫不良反应的重要性，包括神经系统综合征，如脑炎，用ICIs治疗癌旁病变高风险患者时。此外,该病例显示随着时间的推移自身抗体的发展。
■我们描述了一位72岁的男性小细胞肺癌患者，在Durvalumab辅助治疗期间,患者出现了GABABR1和GAD65抗体,同时出现了糖尿病和自身免疫性边缘叶脑炎.因为作为治疗研究的一部分，他被前瞻性地追踪，在发展为脑炎和糖尿病之前，随着时间的推移，我们可以获得重复的血清样本和认知评估，除了以后的评估。高滴度的GABABR1抗体出现早期，而GAD65抗体出现较晚，滴度较低，与糖尿病的发展平行。当他随后出现脑炎的临床症状时，通过脑电图和脑部MRI证实，他也有CSFGABABABR1抗体.停用Durvalumab，并开始随后血浆置换的类固醇治疗，导致CSF和血清抗体水平降低。脑炎的临床体征逐渐好转。
■此案例说明了意识到可能的严重自身免疫不良反应的重要性，包括神经系统综合征，如脑炎，用ICIs治疗癌旁病变高风险患者时。此外,该病例显示随着时间的推移自身抗体的发展。
