Nivolumab, an anti-programmed death-1 (PD-1) receptor monoclonal antibody, has proven effective in treating platinum-resistant metastatic head and neck squamous cell carcinoma. Immune-related adverse events (irAEs) are well-known complications of PD-1 inhibitors. Meanwhile, cytokine release syndrome (CRS), a life-threatening immune-related adverse event, rarely develops due to nivolumab monotherapy. Here, we report a case of a 65-year-old man with squamous cell head and neck carcinoma of an occult primary origin who developed nivolumab-associated late-onset CRS that recurred. The patient was admitted with symptoms of fatigue, fever, hypotension, and respiratory distress. The diagnosis of CRS was supported by the elevated serum levels of interleukin-6 and ferritin, and the patient responded well to high-dose methylprednisolone. CRS recurred during steroid tapering, coinciding with an increased tumor burden
however, it was successfully managed with increased steroid dosing. Early detection and treatment with steroids are essential for the management of CRS.