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

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.

Keywords: NSCLC; Nivolumab; PD-1 antibody; SMARCA4; SWI/SNF complex.

Figure 1

(a–f) Histopathological and immunohistochemical findings of the primary lung tumor (x40). (a,b) Hematoxylin and eosin (H&E) staining shows a poorly differentiated carcinoma and a partly glandular structure. (c) TTF‐1 (SP141), (d) SMARCA2 (HPA029981), (e) SMARCA4 (EPNCIR111A), and (f) PD‐L1 (28‐8).

Figure 2

Chest computed tomography images: (a) Baseline before nivolumab treatment; (b) partial response after four doses of nivolumab; and (c) after 22 doses of nivolumab.