Cytokine Release Syndrome: Current Perspectives

Figures & data

Table 1 Risk Factors For Development Of Severe CRS

Risk Factors For Severe CRS
Early onset of CRS (within 72 hrs)
High disease burden
Lymphodepletion with flurarabine-based conditioning
High infused CAR-T cell dose
Severe thrombocytopenia
CART cells without selection of CD8^+ central memory T cells
High baseline serum ferritin (>1500 µg/L)

Table 2 Selected CAR-T Trials Reporting CRS Incidence, Grading And Treatment

Trial	Publication Type	CRS Incidence (All Grades)	CRS Grade 3–4	CRS Grading Scale Used	Tocilizumab/Corticosteroid Usage*
ZUMA-1^Citation1	Manuscript	94%	13%	Lee Criteria	43%/27%
JULIET	Manuscript^Citation2	58%	22%	UPenn	15%/11%
	Abstract^Citation32	57%	17%	Lee Criteria
NHL 001^Citation73	Abstract	35%	1%	Lee Criteria	21%/21%
BB2121^Citation4	Manuscript	76%	6%	Lee Criteria	21%/12%
Axi-cel Real world experience^Citation74	Abstract	92%	7%	Lee Criteria	62%/57%

Note: *Corticosteroid usage for CRS, ICANS or both.

Table 3 Current Clinical Trials For Prevention Or Treatment Of CRS

Trial Number	Study	Status	Inclusion Criteria	Intervention
NCT02906371	A Two Cohort Pilot Study of Tocilizumab Optimization Timing for CAR-T19-Associated CRS Management in Pediatric Patients With CD19 Expressing Relapsed/Refractory B-cell ALL	Active, not recruiting Two cohorts, open-label, phase1/2 study	Pediatric patients aged 1–24 years with CD19 expressing relapsed/refractory B-cell ALL	Two cohorts defined based upon pre-infusion high versus low tumor burden: 1. High tumor burden cohort (high risk of severe CRS) to receive earlier administration of tocilizumab for CRS 2. Low tumor burden cohort (low risk of severe CRS) to receive standard timing of tocilizumab for CRS
NCT04048434	Effectivity of Extracorporeal Cytokine Adsorption (Cytosorb) as Additive Treatment of CAR-T Cell-Associated Cytokine Release (CRS) Syndrome and Encephalopathy Syndrome (CRES)	Not yet recruiting	Patients aged 18 or older who develop severe CRS (>3)/severe CRES (>3) and CRS/CRES onset <6 hrs.	Patients with severe CAR-T cell-associated CRS (defined as vasopressor dependent) will be treated with standard of care + cytokine adsorption (6 hourly for 24 hrs.).
NCT03696784	A Phase I Study of Autologous Activated T-cells Targeting the CD19 Antigen and Containing Inducible Caspase 9 Safety Switch (iC9-CAR19) in Subjects With Relapsed/Refractory B-cell Lymphoma	Recruiting Phase I	Patients aged 18 or older with relapsed or refractory B-cell Lymphoma	Patients who develop grade 4 CRS or grade ≥3 CRS or who develop grade ≥3 CRES or grade 2 CRES that is unresponsive to standard of care interventions will be given Rimiducid at 0.4 mg/kg.
NCT03016377	Administration of Autologous CAR-T Cells Targeting the CD19 Antigen and Containing the Inducible Caspase9 Safety Switch in Patients With (iC9-CAR19) Relapsed/Refractory ALL	Recruiting Phase I	Patients aged 3–70 years with relapsed or refractory B-cell ALL	Patients who develop grade 4 CRS or grade 2/3 CRS that is unresponsive to standard of care interventions will be given Rimiducid at 0.4 mg/kg.
NCT04071366	A Study of Itacitinib for the Prevention of Cytokine Release Syndrome Induced by Immune Effector Cell Therapy	Study to open in January 2020 Phase 2	Patients 12 years and older eligible to receive either tisagenlecleucel or axicabtagene ciloleucel for approved hematologic indications	Oral administration of itacitinib 200 mg once daily for 30 days for the prevention of CRS

Note: Source: from ClinicalTrials.Gov (accessed on October 1, 2019).

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