Successful continuous nivolumab therapy for metastatic non-small cell lung cancer after local treatment of oligometastatic lesions

Abstract

The patient in this report was a 57-year-old man with metastatic non-small cell lung cancer (NSCLC). After no response to two lines of systemic chemotherapy, he was treated with nivolumab as third-line therapy, which resulted in a partial response. After 17 months of nivolumab treatment, he developed bone metastasis in his left femur which was treated with radiation therapy. Nivolumab was restarted after radiation therapy. Four months after radiation therapy, he developed another metastatic lesion in the small intestine which was surgically resected. Because there were no recurrent NSCLC lesions after surgical resection, nivolumab was restarted again. At 18 months after surgery, there were no recurrent NSCLC lesions. Immunohistochemical analysis of peritumoral T lymphocytes showed higher expression of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) and lymphocyte activation gene 3 (LAG-3) in recurrent lesions of bone and small intestine than in primary lesions. Upregulation of TIM-3 and LAG-3 could be associated with mechanisms of adaptive resistance to nivolumab in this case. Here, we report a successful case of continued nivolumab therapy with remission after local treatments consisting of radiation therapy and surgical resection for oligometastases. Continuation of immune checkpoint inhibitor (ICI) treatment may be worth considering if oligometastases can be controlled. KEY POINTS: Significant findings of the study We report a successful case of continued nivolumab treatment with remission after local treatment (radiation therapy and surgical resection) for oligometastases. What this study adds Upregulation of T cell immunoglobulin and mucin domain-containing protein 3 and lymphocyte-activation gene 3 could be associated with mechanisms of adaptive resistance to nivolumab.

Keywords: Adaptive resistance; T cell immunoglobulin and mucin domain-containing protein 3; immune checkpoint inhibitors; local treatment; lymphocyte-activation gene 3.