TY - JOUR
T1 - Modified EASIX predicts severe cytokine release syndrome and neurotoxicity after chimeric antigen receptor T cells
AU - Pennisi, Martina
AU - Sanchez-Escamilla, Miriam
AU - Flynn, Jessica R.
AU - Shouval, Roni
AU - Tomas, Ana Alarcon
AU - Silverberg, Mari Lynn
AU - Batlevi, Connie
AU - Brentjens, Renier J.
AU - Dahi, Parastoo B.
AU - Devlin, Sean M.
AU - Diamonte, Claudia
AU - Giralt, Sergio
AU - Halton, Elizabeth F.
AU - Jain, Tania
AU - Maloy, Molly
AU - Mead, Elena
AU - Palomba, Maria Lia
AU - Ruiz, Josel
AU - Santomasso, Bianca
AU - Sauter, Craig S.
AU - Scordo, Michael
AU - Shah, Gunjan L.
AU - Park, Jae H.
AU - San Segundo, Lucrecia Yanez
AU - Perales, Miguel Angel
N1 - Publisher Copyright:
© 2021 by The American Society of Hematology
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85115339187&partnerID=8YFLogxK
U2 - 10.1182/BLOODADVANCES.2020003885
DO - 10.1182/BLOODADVANCES.2020003885
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C2 - 34432870
AN - SCOPUS:85115339187
SN - 2473-9529
VL - 5
SP - 3397
EP - 3406
JO - Blood advances
JF - Blood advances
IS - 17
ER -