CytoSorbents Corporation (CTSO)

[techxen]

2nd published case report of CAR-T CRS treatment

I believe this is the second case published. The first was in the press release dated February 5 and was published in the journal, Critical Care Explorations, a publication of the Society of Critical Care Medicine, of a 14-year old boy with refractory acute lymphoblastic leukemia. I ran across this one today in the Journal of Critical Care which was dated February 19, 2020. It was of a 65?years old male who developed grade 4 CRS with refractory shock after CAR-T application.

https://www.sciencedirect.com/science/article/abs/pii/S0883944119318313

What was interesting is at the end of the article they said that the Extracorporeal Cytokine Adsorption as Additive Treatment of CAR-T Associated Cytokine Release Syndrome (CRS) (CYTORELEASE)trial which is being run out of Hannover in Germany is recruiting, yet on the ClinicalTrials web site it shows they have not started recruiting yet - maybe the web site has not yet been updated to reflect this.

Extracorporeal cytokine removal in severe CAR-T cell associated cytokine release syndrome

Abstract

Purpose

Life-threatening complications of CD-19 Chimeric antigen receptor - T (CAR-T) cells such as the cytokine release syndrome (CRS)) have been reported. Treatment is limited to IL-6 blockade and steroids although global removal of elevated soluble inflammatory factors might be more effective.

Methods

Clinical course of a CRS patient treated with extracorporeal cytokine adsorption (Cytosorb®). A panel of 48 cytokines, chemokines and endothelial markers has been analyzed longitudinally. Ex vivo stimulation of endothelial cells to visualize (immunocytochemistry) and quantify (ECIS, TER) endothelial barrier effects.

Results

Following CAR-T cell application a 65?years old male developed grade 4 CRS with refractory shock (3 vasopressors) and severe capillary leakage (+37?L/24?h resuscitation). Treatment included IL-6 blockade, methylprednisolone and additionally Cytosorb hemoperfusion. While multiple soluble inflammatory factors were elevated and most of them decreased by more than 50% following Cytosorb, markers of endothelial injury increased steadily (e.g. Angpt-2/Angpt-1) leading to profound endothelial activation and leakage in ex vivo assays.
Conclusion

This is the first reported use of cytokine adsorption for CRS showing efficacy in absorption of various cytokines but not endothelial growth factors. A randomized controlled trial to evaluate additional Cytosorb treatment in CRS is currently recruiting at our institution (NCT04048434).

https://clinicaltrials.gov/ct2/show/NCT04048434