Relapsing cytokine release syndrome in a patient with metastatic renal cell carcinoma treated with pembrolizumab and axitinib therapy

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Abstract
As immune checkpoint inhibitors become more widely available, the optimal management of immune-related adverse events (irAEs) is becoming increasingly important. Although irAEs are diverse, reports on cytokine release syndrome are rare. Here, we report a case of a 48-year-old man with relapsing cytokine release syndrome after receiving pembrolizumab and axitinib combination therapy for metastatic renal cell carcinoma. During dose reduction of prednisolone for immune-related hepatitis on day 33 after starting pembrolizumab plus axitinib, the patient suddenly developed abdominal pain, and a few hours later became hypotensive and poorly oxygenated. Despite the use of a ventilator and high doses of catecholamines, blood pressure and oxygenation could not be maintained. Extracorporeal membrane oxygenation and intra-aortic balloon pumping were also administered. The cytokine release syndrome (CRS) was treated with tocilizumab, and his general condition improved. Lower-grade CRS relapsed four times despite a moderate dose of oral prednisolone with mycophenolate mofetil or tacrolimus. After gradual reduction in prednisolone over 5 months, the patient was discharged from the hospital. Partial remission of renal cell carcinoma continued for 21 months, and salvage radical nephrectomy was performed. The patient remained disease-free without the need for further treatment 9 months after surgery.

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