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妥协还是不妥协?低剂量甲基强的松龙和双环醇成功治疗非小细胞肺癌患者因帕利珠单抗引起的肝炎 1 例报告。

Compromise or not? A case report of successful treatment of pembrolizumab-induced hepatitis in a patient with non-small cell lung cancer with low-dose methylprednisolone and bicyclol.

机构信息

Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, Beijing, China.

Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.

出版信息

Thorac Cancer. 2020 Jul;11(7):2023-2030. doi: 10.1111/1759-7714.13463. Epub 2020 May 7.

Abstract

Pembrolizumab, an anti-programmed cell death protein 1 (PD-1) antibody, has been shown to improve survival in patients with non-small cell lung cancer (NSCLC) with high expression of programmed death-ligand 1 (PD-L1). Corticosteroids are the mainstay for most high-grade immune-related adverse events (irAEs) such as pembrolizumab-induced hepatitis. However, the dose and duration of corticosteroid therapy are not well defined. The objective of this case report was to describe a new treatment pattern for severe immune checkpoint inhibitor-associated hepatitis. Here, we report the case of a patient with metastatic lung adenocarcinoma who developed grade 3 immunotherapy-induced hepatitis after the first cycle of pembrolizumab. Alanine aminotransferase (ALT) levels peaked at 233 U/L. Hepatitis was alleviated after the administration of methylprednisolone. Therefore, we retreated the patient with pembrolizumab. However, aminotransferase levels increased again after the initiation of low-dose methylprednisolone or the reuse of pembrolizumab. Finally, hepatitis was controlled with low-dose methylprednisolone plus bicyclol, a Chinese hepatoprotective agent. Although the patient had been on low-dose methylprednisolone therapy for about six months, he showed a prompt response. During this period, we also found a dramatic decrease in the neutrophil-lymphocyte ratio (NLR), senescent T cells (CD8 CD28 CD57 ), and myeloid-derived suppressor cells (MDSCs) in the peripheral blood of the patient. To our knowledge, this is the first case report of successful management of grade 3 pembrolizumab-induced hepatitis with a combination of low-dose corticosteroids and bicyclol. The durable clinical response and changes in blood biomarkers indicate that low doses of corticosteroids do not compromise the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this case may provide a new treatment pattern for severe immunotherapy-induced hepatitis.

摘要

派姆单抗是一种抗程序性细胞死亡蛋白 1(PD-1)抗体,已被证明可提高高表达程序性死亡配体 1(PD-L1)的非小细胞肺癌(NSCLC)患者的生存率。皮质类固醇是大多数高级免疫相关不良事件(irAE)的主要治疗药物,如派姆单抗诱导的肝炎。然而,皮质类固醇治疗的剂量和持续时间尚未确定。本病例报告的目的是描述一种新的治疗方案,用于治疗严重的免疫检查点抑制剂相关肝炎。在这里,我们报告了一例转移性肺腺癌患者的病例,该患者在接受派姆单抗第一周期治疗后发生 3 级免疫治疗诱导的肝炎。丙氨酸氨基转移酶(ALT)水平峰值为 233 U/L。给予甲基强的松龙后,肝炎得到缓解。因此,我们重新给患者使用派姆单抗。然而,在低剂量甲基强的松龙或重新使用派姆单抗开始后,转氨酶水平再次升高。最后,使用低剂量甲基强的松龙加保肝药双环醇控制了肝炎。虽然患者接受低剂量甲基强的松龙治疗约 6 个月,但他反应迅速。在此期间,我们还发现患者外周血中性粒细胞-淋巴细胞比值(NLR)、衰老 T 细胞(CD8 CD28 CD57)和髓源抑制细胞(MDSCs)明显下降。据我们所知,这是首例成功使用低剂量皮质类固醇和双环醇联合治疗 3 级派姆单抗诱导性肝炎的病例报告。持久的临床反应和血液生物标志物的变化表明,低剂量皮质类固醇不会影响免疫检查点抑制剂(ICIs)的疗效。因此,这种情况可能为严重免疫治疗诱导性肝炎提供一种新的治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e139/7327908/afeacd1d881c/TCA-11-2023-g001.jpg

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