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帕博利珠单抗单药治疗一名PD-L1阴性、肿瘤突变负荷高且肿瘤浸润淋巴细胞阳性的非小细胞肺癌患者后完全缓解:一例报告

Complete remission after pembrolizumab monotherapy in a non-small cell lung cancer patient with PD-L1 negative, high tumor mutational burden, and positive tumor-infiltrating lymphocytes: A case report.

作者信息

Li Suoni, Ma Jiequn, Bai Jie, Zhao Zheng

机构信息

Department of Oncology, Shaanxi Provincial Tumor Hospital, Xi'an, Shaanxi, China.

出版信息

Medicine (Baltimore). 2024 Dec 6;103(49):e40369. doi: 10.1097/MD.0000000000040369.

DOI:10.1097/MD.0000000000040369
PMID:39654211
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11630958/
Abstract

RATIONALE

Immune checkpoint inhibitors have been used to treat cancer patients. Non-small cell lung cancer (NSCLC) patients with a high expression level of programmed cell death ligand-1 (PD-L1) could benefit from immune checkpoint inhibitor monotherapy. However, treating NSCLC patients with PD-L1 negative is still a clinical challenge. The utilization of new-type tumor markers as predictive indicators of therapeutic efficacy, with the aim of guiding clinical medication strategies, has emerged as a paramount focus of clinical investigation and interest.

PATIENT CONCERNS AND DIAGNOSES

We reported a 72-year-old male with cough diagnosed as poorly differentiated metastatic lung adenocarcinoma (cT3N2M1, stage IV). He tested negative for driver gene mutations, and PD-L1 negative (<1%), but a high tumor mutational burden (30.9 and 39.1 mutations/Mb in the lung tissue and blood, respectively), and positive tumor-infiltrating lymphocytes.

INTERVENTIONS

The patient received pembrolizumab monotherapy.

OUTCOMES

After 8 treatment cycles over 5 months, repeat examinations showed significantly reduced lung mass and circulating tumor DNA abundance. The patient reached clinical complete remission and had long-term survival with no significant adverse events.

LESSONS

A comprehensive evaluation of multiple tumor biomarkers should be considered in NSCLC patients. Pembrolizumab monotherapy could benefit NSCLC patients with negative driver genes, PD-L1 negative, a high tumor mutational burden, and positive tumor-infiltrating lymphocytes.

摘要

原理

免疫检查点抑制剂已被用于治疗癌症患者。程序性细胞死亡配体-1(PD-L1)高表达水平的非小细胞肺癌(NSCLC)患者可从免疫检查点抑制剂单药治疗中获益。然而,治疗PD-L1阴性的NSCLC患者仍然是一项临床挑战。利用新型肿瘤标志物作为治疗疗效的预测指标,以指导临床用药策略,已成为临床研究和关注的首要焦点。

患者关注与诊断

我们报告了一名72岁男性,因咳嗽被诊断为低分化转移性肺腺癌(cT3N2M1,IV期)。他的驱动基因突变检测为阴性,PD-L1阴性(<1%),但肿瘤突变负荷高(肺组织和血液中的突变分别为30.9和39.1个/Mb),且肿瘤浸润淋巴细胞阳性。

干预措施

患者接受帕博利珠单抗单药治疗。

结果

经过5个月的8个治疗周期后,复查显示肺部肿块和循环肿瘤DNA丰度显著降低。患者达到临床完全缓解,长期存活且无明显不良事件。

经验教训

NSCLC患者应考虑对多种肿瘤生物标志物进行综合评估。帕博利珠单抗单药治疗可使驱动基因阴性、PD-L1阴性、肿瘤突变负荷高且肿瘤浸润淋巴细胞阳性的NSCLC患者获益。

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Immune Checkpoint Inhibitors in Cancer Therapy.癌症治疗中的免疫检查点抑制剂。
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PD-1 and PD-L1 in cancer immunotherapy: clinical implications and future considerations.PD-1 和 PD-L1 在癌症免疫治疗中的作用:临床意义和未来思考。
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