Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction. CRS is most often associated with chimeric antigen receptor (CAR)-T cell therapy, but it also occurs in association with bispecific T cell engager therapy, other monoclonal antibody-based therapy, haploidentical ...

2020年4月9日 · This study is the first to assess concordance between 3 CRS grading scales using the same patient data set and to compare tocilizumab use according to the Lee scale in the JULIET trial and the ZUMA-1 (Long-Term Safety and Activity of Axicabtagene Ciloleucel in Refractory Large B-Cell Lymphoma) trial.

CRS is “a supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells. Symptoms can be progressive, must include fever at the onset and may include hypotension, capillary leak (hypoxia) and end organ dysfunction.”

The Penn grading scale demonstrates how patients with grade 2 vs grade 3 vs grade 4 CRS differ, as supported by the differences in time to onset and duration of CRS, duration of high fevers, frequency of hypotension requiring vasopressors, and need for anti-cytokine therapy.

Aggressive intervention required for response: oxygen requirement ≥40%, hypotension requiring high dose/multiple pressors, grade 3 organ toxicity, or grade 4 transaminitis

Grade 3 CRS includes oxygen supplementation at ≥40% FiO 2 for the management of confirmed hypoxia, hypotension requiring high-dose or multiple vasopressors, grade 4 transaminitis, or other grade 3 organ toxicity.

GRADE 3 MANAGEMENT Tocilizumab 8 mg/kg (Consider alternative agents after 2 doses) *No more than 3 doses in a 24 hr period or 4 doses in total. Dexamethasone (10 mg q12-24 hrs) with tocilizumab initial tocilizumab. For patients refractory to dexamethasone can increase to …

CAR T-cell Grading and Management: Cytokine Release Syndrome

# CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. For example, a patient with temperature of 39.5°C, hypotension requiring one vasopressor, and hypoxia requiring low-flow nasal cannula is classified as grade 3 CRS.

The CTCAE grading of CRS was initially developed for CRS related to blinatumomab infusion. The Lee and Neelapu grading systems allowed low-dose vasopressors and low requirement for oxygen (< 40%) as grade 2, whereas the Penn grading scale placed those to grade 3 when IV fluid resuscitation, any vasopressors, and/or oxygen is required.