Modified EASIX predicts severe cytokine release syndrome and neurotoxicity after chimeric antigen receptor T cells Journal Article
| Authors: | Pennisi, M.; Sanchez-Escamilla, M.; Flynn, J. R.; Shouval, R.; Alarcon Tomas, A.; Silverberg, M. L.; Batlevi, C.; Brentjens, R. J.; Dahi, P. B.; Devlin, S. M.; Diamonte, C.; Giralt, S.; Halton, E. F.; Jain, T.; Maloy, M.; Mead, E.; Palomba, M. L.; Ruiz, J.; Santomasso, B.; Sauter, C. S.; Scordo, M.; Shah, G. L.; Park, J. H.; Yanez San Segundo, L.; Perales, M. A. |
| Article Title: | Modified EASIX predicts severe cytokine release syndrome and neurotoxicity after chimeric antigen receptor T cells |
| Abstract: | Patients who develop chimeric antigen receptor (CAR) T-cell-related severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) exhibit hemodynamic instability and endothelial activation. The EASIX (Endothelial Activation and Stress Index) score (lactate dehydrogenase [LDH; U/L] 3 creatinine [mg/dL]/platelets [PLTs; 109 cells/L]) is a marker of endothelial damage that correlates with outcomes in allogeneic hematopoietic cell transplantation. Elevated LDH and low PLTs have been associated with severe CRS and ICANS, as has C-reactive protein (CRP), while increased creatinine is seen only in a minority of advanced severe CRS cases. We hypothesized that EASIX and 2 new modified EASIX formulas (simplified EASIX, which excludes creatinine, and modified EASIX [m-EASIX], which replaces creatinine with CRP [mg/dL]), calculated peri-CAR T-cell infusion, would be associated with development of severe (grade $ 3) CRS and ICANS. We included 118 adults, 53 with B-acute lymphoblastic leukemia treated with 1928z CAR T cells (NCT01044069) and 65 with diffuse large B-cell lymphoma treated with axicabtagene ciloleucel or tisagenlecleucel. The 3 formulas showed similar predictive power for severe CRS and ICANS. However, low PLTs and high CRP values were the only variables individually correlated with these toxicities. Moreover, only m-EASIX was a significant predictor of disease response. m-EASIX could discriminate patients who subsequently developed severe CRS preceding the onset of severe symptoms (area under the curve [AUC] at lymphodepletion, 80.4%; at day 21, 73.0%; and at day 11, 75.4%). At day 13, it also had high discriminatory ability for severe ICANS (AUC, 73%). We propose m-EASIX as a clinical tool to potentially guide individualized management of patients at higher risk for severe CAR T-cell-related toxicities. © 2021 by The American Society of Hematology |
| Journal Title: | Blood Advances |
| Volume: | 5 |
| Issue: | 17 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2021-09-14 |
| Start Page: | 3397 |
| End Page: | 3406 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2020003885 |
| PUBMED: | 34432870 |
| PROVIDER: | scopus |
| PMCID: | PMC8525234 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2021 -- Source: Scopus |
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