Response to nivolumab as an immune checkpoint inhibitor rechallenge for esophageal squamous cell carcinoma with PD-L1 amplification: a case report

The Programmed death-ligand 1 (PD-L1) gene amplification has been proposed as a potential predictive biomarker for the efficacy of immune checkpoint inhibitors (ICIs); however, its clinical relevance in the setting of ICI rechallenge after resistance to initial ICI therapy remains unclear. We report a case of metastatic esophageal squamous cell carcinoma (ESCC) with PD-L1 gene amplification that showed a partial response (PR) to nivolumab monotherapy as an ICI rechallenge. A 61-year-old man with clinical stage III ESCC underwent curative esophagectomy followed by neoadjuvant chemotherapy. Three years after surgery, mediastinal lymph node recurrence was detected, and the patient was treated with curative chemoradiotherapy followed by maintenance anti-PD-L1 antibody therapy. During maintenance treatment, a new recurrence developed in the right supraclavicular lymph node. Despite multiple subsequent lines of chemotherapy, the disease progressed. Comprehensive genomic profiling revealed amplification of CD274 (PD-L1) with a copy number gain of 8. In addition, immunohistochemical analysis using the PD-L1 IHC 22C3 pharmDx assay demonstrated high PD-L1 expression, with a combined positive score exceeding 40. Based on these findings, nivolumab was administered as an ICI rechallenge 8.8 months after discontinuation of the initial ICI therapy. The patient achieved a PR after 3.1 months of nivolumab treatment, although disease progression was observed after 5 months. Although limited by its single-patient nature, this report suggests that PD-L1 gene amplification may represent complementary biological information associated with the efficacy of ICI rechallenge, warranting further investigation in larger cohorts.