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培普利珠单抗,一种程序性死亡受体-1 单克隆抗体,治疗后复发霍奇金淋巴瘤患者出现自身免疫性溶血性贫血。

Autoimmune hemolytic anemia in patients with relapsed Hodgkin's lymphoma after treatment with penpulimab, a monoclonal antibody against programmed death receptor-1.

机构信息

Department of Intensive Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hankou, 430030, Wuhan, China.

Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hankou, 430030, Wuhan, China.

出版信息

Invest New Drugs. 2022 Aug;40(4):854-857. doi: 10.1007/s10637-022-01254-2. Epub 2022 May 3.

Abstract

In August 2021, penpulimab, an anti-programmed cell death 1 (PD-1) monoclonal antibody, was approved in China for the treatment of adult patients with relapsed or refractory classic Hodgkin's lymphoma who completed at least second-line chemotherapy. Penpulimab is currently in clinical trials in China and Australia for the treatment of nasopharyngeal cancer and non-small cell lung cancer. Several clinical studies have shown that penpulimab is safe and effective, and no immune-related adverse events (irAEs) above grade 3 were observed. A 60-year-old woman with relapsed Hodgkin's lymphoma developed nausea and fatigue after receiving penpulimab monotherapy (200 mg every 2 weeks). Ten days after the second injection, the patient's condition worsened, and biochemical test results confirmed autoimmune hemolytic anemia (AIHA), with a hemoglobin level of 70 g/L (normal range, 115-150 g/L), an unconjugated bilirubin level of 19.08 µmol/L (normal range, 0-17 µmol/L), and positive direct antiglobulin test (DAT) results. On the same day, we treated her with prednisone (2 mg/kg), but her hemoglobin level continued to decline to 51 g/L one day after hormone therapy, so she received an intravenous infusion of washed red blood cells and underwent plasmapheresis, which eventually resolved the AIHA. Considering that the hemoglobin level was < 65 g/L and the irAE was grade 4, penpulimab was discontinued, and the symptoms of AIHA disappeared. From this event, we know that severe AIHA can occur after penpulimab use similar to other PD-1 antibodies. In this case, plasmapheresis showed a good therapeutic effect and should be used as a supplementary means when hormonal and immunosuppressive therapies cannot provide rapid symptom relief. In addition, we recommend regular direct antiglobulin testing, as well as haptoglobin, lactate dehydrogenase and other hemolysis-related laboratory tests, in patients prescribed penpulimab and similar drugs for the early diagnosis and treatment of AIHA.

摘要

2021 年 8 月,抗程序性细胞死亡蛋白 1(PD-1)单克隆抗体信迪利单抗在中国获批,用于治疗至少完成二线化疗的复发或难治性经典型霍奇金淋巴瘤成人患者。信迪利单抗目前正在中国和澳大利亚进行临床试验,用于治疗鼻咽癌和非小细胞肺癌。几项临床研究表明,信迪利单抗安全有效,未观察到 3 级及以上免疫相关不良事件(irAEs)。一位 60 岁女性在接受信迪利单抗单药治疗(每 2 周 200mg)后出现恶心和乏力。第二次注射后 10 天,患者病情恶化,生化检测结果证实为自身免疫性溶血性贫血(AIHA),血红蛋白水平为 70g/L(正常范围为 115-150g/L),未结合胆红素水平为 19.08µmol/L(正常范围为 0-17µmol/L),直接抗球蛋白试验(DAT)结果阳性。同日,我们给予患者泼尼松(2mg/kg)治疗,但激素治疗后 1 天患者血红蛋白水平持续下降至 51g/L,因此输注洗涤红细胞并进行血浆置换,最终缓解 AIHA。考虑到血红蛋白水平<65g/L,irAE 为 4 级,停用信迪利单抗,AIHA 症状消失。由此可知,信迪利单抗与其他 PD-1 抗体类似,使用后可能发生严重 AIHA。在这种情况下,血浆置换显示出良好的治疗效果,在激素和免疫抑制治疗不能迅速缓解症状时,应作为补充手段。此外,我们建议定期进行直接抗球蛋白检测,以及结合珠蛋白、乳酸脱氢酶等溶血性相关实验室检测,以用于接受信迪利单抗和类似药物治疗的患者,从而早期诊断和治疗 AIHA。

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