Cytokine release syndrome (CRS)
Cytokine release syndrome is a systemic inflammatory reaction after strong immune-cell activation, for example by T-cell engaging antibodies or CAR-T cells. It is graded by severity and is the reason for step-up dosing.
Definition
Cytokine release syndrome (CRS) is a systemic inflammatory reaction that follows strong activation of immune cells, with release of cytokines. It occurs with T-cell engaging bispecific antibodies and CAR-T cells. Typical signs are fever and, when more severe, low blood pressure and low oxygen; severity is graded, commonly with the ASTCT consensus grading.
Link to dosing
CRS is most common after the first dose of a T-cell engager. Step-up dosing starts with a low dose to lower the first concentration peak and increases it over the first cycle.
What PK can and cannot say
A population PK model can show how the first dose, the step size and the interval change exposure. It does not by itself tell how much less CRS occurs: that needs a validated link from PK to receptor occupancy and from occupancy to CRS.
On this site
The mosunetuzumab reimplementation computes how changed regimens alter the first peak and the exposure, and examines the published occupancy–CRS regression as an exploratory output rather than a validated clinical prediction. See also receptor occupancy. Management is described in each product's labeling and is outside the scope of this site.
Frequently asked questions
Does a lower first peak mean less CRS?
It is the intention of step-up dosing, but PK alone does not show how much less CRS occurs; that needs validated links from PK to receptor occupancy and from occupancy to CRS.
How is CRS graded?
By severity, commonly with the ASTCT consensus grading, which uses fever, blood pressure and oxygen requirement.