Cytokine release syndrome: Who is at risk and how to treat.

T-cell engaging therapies such as blinatumomab and anti-CD19 chimeric antigen receptor (CAR) T cells have revolutionized our approach to patients with relapsed and refractory acute lymphoblastic leukemia (ALL). However, the immune activation responsible for high remission rates is also responsible for the unique treatment-related toxicity of cytokine release syndrome (CRS). The clinical signs of CRS include fever, hemodynamic instability, and capillary leak, which correlate with T-cell activation and elevated cytokine levels. Tocilizumab, an anti-IL-6 receptor antagonist, provides control of severe CRS induced by CAR T cells without being directly T cell toxic. With blinatumomab, the approach to CRS has been largely preventative with administration strategies that include disease cytoreduction, corticosteroid premedication, and dose titration.