A Case of Cytokine Release Syndrome Induced by Avelumab and Axitinib Combination Therapy for Metastatic Renal Cell Carcinoma

Introduction Cytokine release syndrome (CRS) is a rare immune‐related adverse event of immune checkpoint inhibitors (ICIs). At present, its association with avelumab–axitinib therapy for renal cell carcinoma (RCC) has yet to be reported. Differentiating early CRS from an infusion‐related reaction (IRR) is clinically challenging, particularly in the context of concurrent coronavirus disease (COVID‐19). Case Presentation A 76‐year‐old woman with recurrent RCC developed chills, hypotension requiring norepinephrine, and hypoxemia within hours of her first avelumab infusion. Despite IRR‐directed therapy, the patient's condition worsened. Laboratory evaluation revealed markedly elevated Interleukin‐6 with normal C‐reactive protein, elevated procalcitonin levels, and negative cultures, supporting cytokine‐driven inflammation. COVID‐19 was detected and the clinical trajectory suggested CRS amplification. The patient was successfully treated with corticosteroids and tocilizumab. Conclusion This is the first report of CRS associated with avelumab–axitinib therapy in RCC and highlights the importance of early recognition and distinction from IRR, especially when COVID‐19 coexists.