Figure 3
Figure 3. Cytokine changes associated with clinical findings in a hypothetical patient with grade 3 CRS. A dramatic rise in IL-6 and IFNγ levels is associated with the onset of fever at day 3 after CAR T-cell infusion. Despite vigilant supportive care, the patient becomes hypotensive, requiring the use of 1 vasopressor on day 5. After a brief period of cardiovascular stability, a second vasopressor is required to maintain adequate perfusion on day 6, at which time tocilizumab is administered. IL-6 levels continue to rise transiently after tocilizumab, because it continues to be produced and tocilizumab blocks IL-6R-mediated endocytosis. Vasopressor support is gradually weaned over the next 48 hours, although neurologic changes may persist or initially manifest after tocilizumab, but eventually resolve. Several other inflammatory cytokines, including TNFα, IL-2, GM-CSF, and others noted in the text are also likely to be elevated during the peak of the syndrome.

Cytokine changes associated with clinical findings in a hypothetical patient with grade 3 CRS. A dramatic rise in IL-6 and IFNγ levels is associated with the onset of fever at day 3 after CAR T-cell infusion. Despite vigilant supportive care, the patient becomes hypotensive, requiring the use of 1 vasopressor on day 5. After a brief period of cardiovascular stability, a second vasopressor is required to maintain adequate perfusion on day 6, at which time tocilizumab is administered. IL-6 levels continue to rise transiently after tocilizumab, because it continues to be produced and tocilizumab blocks IL-6R-mediated endocytosis. Vasopressor support is gradually weaned over the next 48 hours, although neurologic changes may persist or initially manifest after tocilizumab, but eventually resolve. Several other inflammatory cytokines, including TNFα, IL-2, GM-CSF, and others noted in the text are also likely to be elevated during the peak of the syndrome.

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