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程序性细胞死亡受体-1(PD-1)抑制剂治疗非小细胞肺癌患者后的结核病。病例报告及文献复习。

Tuberculosis following programmed cell death receptor-1 (PD-1) inhibitor in a patient with non-small cell lung cancer. Case report and literature review.

机构信息

Department of internal medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.

Department of Medical Oncology, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar.

出版信息

Cancer Immunol Immunother. 2021 Apr;70(4):935-944. doi: 10.1007/s00262-020-02726-1. Epub 2020 Oct 17.

Abstract

Immune checkpoint inhibitors (ICIs)-anti-programmed death-1 (PD-1) and their ligands (PD-L1 and PD-L2) have become widely used in the treatment of several malignancies. Many immune-related adverse events (irAEs) have been linked to these agents. Nonetheless, tuberculosis (TB) reactivation during their use is increasingly recognized and reported. Herein, we present a 58-year-old lady with advanced non-small cell lung cancer (NSCLC) ALK-negative, EGFR wild, and PD-L1 immune histochemistry (IHC) strongly positive in 95% of tumor cells, on ongoing treatment with Pembrolizumab as a first-line monotherapy. Our patient presented with 1-week history of productive cough and high-grade fever. Further workup yielded the diagnosis of pulmonary tuberculosis after her Pembrolizumab sixth cycle with positive AFB smear and TB PCR from BAL (rifampin resistance not detected), with negative HIV status. Hence, immunotherapy was held, and patient was commenced on anti-TB regimen. History revealed contact with active TB patient over the past decade, without previous documentation of latent TB or previous TB infection. Her sputum AFB smear remained persistently positive 4 weeks through anti-TB regimen course. Later, the patient was discharged after her sputum was cleared from AFB (two negative sets). In light of pembrolizumab mechanism of action as an immune checkpoint inhibitor, we suspected its implication on reactivating latent TB which was observed in our patient demonstrating features of pulmonary tuberculosis. She was not re-challenged with Pembrolizumab following TB diagnosis.

摘要

免疫检查点抑制剂(ICIs)-抗程序性死亡受体-1(PD-1)及其配体(PD-L1 和 PD-L2)已广泛用于治疗多种恶性肿瘤。许多与免疫相关的不良反应(irAEs)与这些药物有关。尽管如此,在使用这些药物期间,结核病(TB)的再激活越来越受到关注和报道。在此,我们报告了一例 58 岁的晚期非小细胞肺癌(NSCLC)ALK 阴性、EGFR 野生型和 PD-L1 免疫组织化学(IHC)强阳性(肿瘤细胞中 95%阳性)的患者,正在接受 Pembrolizumab 作为一线单药治疗。该患者在接受 Pembrolizumab 第六个周期后出现了 1 周的有痰咳嗽和高热病史。进一步的检查在她的 BAL 中发现了 AFB 涂片阳性和 TB PCR 阳性(未检测到利福平耐药),同时 HIV 检测为阴性,最终诊断为肺结核。因此,停止了免疫治疗,并开始了抗结核治疗方案。患者有过去十年接触活动性结核患者的病史,但没有潜伏性结核或既往结核感染的记录。她的痰 AFB 涂片在抗结核治疗方案的 4 周内持续阳性。在经过两个疗程的抗结核治疗后,她的痰 AFB 转为阴性。随后,患者在痰中清除 AFB(两次阴性)后出院。鉴于 Pembrolizumab 作为免疫检查点抑制剂的作用机制,我们怀疑其在激活潜伏性 TB 方面的作用,这在我们的患者中表现为肺结核的特征。在诊断为结核病后,该患者未再接受 Pembrolizumab 治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5403/10991422/6d1ccb711736/262_2020_2726_Fig1_HTML.jpg

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