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(R)). 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).
- Stahl, K.
- Schmidt, B. M. W.
- Hoeper, M. M.
- Skripuletz, T.
- Mohn, N.
- Beutel, G.
- Eder, M.
- Welte, T.
- Ganser, A.
- Falk, C. S.
- Koenecke, C.
- David, S.
Keywords
- CAR-T-cell
- Cytokine release syndrome
- Extracorporeal cytokine adsorption
- CtoSorbents Corp. Otherwise, the authors declare that they have no competing
- interests.
