Stage 4 Cytokine Release Syndrome Caused by the First Dose of Nivolumab and Ipilimumab Combination Therapy in a Patient with Metastatic Melanoma Successfully Treated with Methylprednisolone, Tocilizumab, and Etanercept

The authors report the first case of stage 4 cytokine release syndrome (CRS) (graded by the National Cancer Institute Common Terminology Criteria for Adverse Effects scale) involving a patient with advanced metastatic melanoma who was treated with the combination of two monoclonal antibodies, nivolumab (anti-programmed cell death receptor 1 inhibitor [PD-1]) and ipilimumab (a cytotoxic T lymphocyte-associated antigen 4 inhibitor [CTLA-4]) after her first dose of both. The patient was treated initially with methylprednisolone and tocilizumab but was refractory to treatment. A trial of etanercept was initiated due to her elevated levels of TNF-α which elicited a satisfactory response. Monoclonal antibody therapy is a new tool for the treatment of many cancers, and therefore there may be a subsequent rise in the cases of CRS and this case exemplifies a treatment algorithm. Utilizing levels of cytokines assists in tailoring treatment such as in this case where etanercept, a TNF-α inhibitor, was utilized due to the patient's elevated levels of TNF-α.