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纳武利尤单抗治疗高肿瘤突变负荷的 SMARCA4 缺陷型非小细胞肺癌成功:一例报告。

Successful treatment with nivolumab for SMARCA4-deficient non-small cell lung carcinoma with a high tumor mutation burden: A case report.

机构信息

Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Division of Pathology, National Cancer Center Hospital East, Kashiwa, Japan.

出版信息

Thorac Cancer. 2019 May;10(5):1285-1288. doi: 10.1111/1759-7714.13070. Epub 2019 Apr 10.

Abstract

SMARCA4 is a subunit of the switch/sucrose non-fermentable (SWI/SNF) chromatin-remodeling complex. An effective treatment for SMARCA4-deficient non-small cell lung carcinoma (NSCLC) has not yet been established. Correlations between a response to immune checkpoint inhibitors and the SWI/SNF complex have been suggested, but little is known about the efficacy of immune checkpoint inhibitors against SMARCA4-deficient NSCLC. A 43-year-old man underwent left upper lobe lung resection and was diagnosed with SMARCA4-deficient lung adenocarcinoma. Two months after surgery, multiple lung metastases appeared. Immunohistochemical analysis showed no PD-L1 expression. Whole-exon sequencing revealed a relatively high tumor mutation burden at 396. After the failure of three standard chemotherapy regimens, the patient was treated with nivolumab as fourth-line treatment. An obvious reduction in the lung metastases was obtained for more than 14 months. We report the first case of SMARCA4-deficient NSCLC with a high tumor mutation burden successfully treated with nivolumab. Anti-PD-1 antibodies might be a promising treatment strategy for patients with SMARCA4-deficient NSCLC.

摘要

SMARCA4 是开关/蔗糖非发酵(SWI/SNF)染色质重塑复合物的一个亚基。尚未建立针对 SMARCA4 缺陷型非小细胞肺癌(NSCLC)的有效治疗方法。免疫检查点抑制剂与 SWI/SNF 复合物之间的相关性已经被提出,但对于免疫检查点抑制剂针对 SMARCA4 缺陷型 NSCLC 的疗效知之甚少。一名 43 岁男性接受了左上肺叶切除术,并被诊断为 SMARCA4 缺陷型肺腺癌。手术后两个月,出现了多个肺转移。免疫组化分析显示 PD-L1 无表达。全外显子组测序显示肿瘤突变负担相对较高,为 396。在三种标准化疗方案失败后,患者接受了nivolumab 作为四线治疗。肺转移得到了超过 14 个月的明显缓解。我们报告了首例成功接受 nivolumab 治疗的 SMARCA4 缺陷型 NSCLC 病例,该病例具有高肿瘤突变负担。抗 PD-1 抗体可能是 SMARCA4 缺陷型 NSCLC 患者有前途的治疗策略。

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