TY - JOUR
T1 - Comparing CAR T-cell toxicity grading systems
T2 - Application of the ASTCT grading system and implications for management
AU - Pennisi, Martina
AU - Jain, Tania
AU - Santomasso, Bianca D.
AU - Mead, Elena
AU - Wudhikarn, Kitsada
AU - Silverberg, Mari Lynne
AU - Batlevi, Yakup
AU - Shouval, Roni
AU - Devlin, Sean M.
AU - Batlevi, Connie
AU - Brentjens, Renier J.
AU - Dahi, Parastoo B.
AU - Diamonte, Claudia
AU - Giralt, Sergio
AU - Halton, Elizabeth F.
AU - Maloy, Molly
AU - Palomba, Maria Lia
AU - Sanchez-Escamilla, Miriam
AU - Sauter, Craig S.
AU - Scordo, Michael
AU - Shah, Gunjan
AU - Park, Jae H.
AU - Perales, Miguel Angel
N1 - Publisher Copyright:
© 2020 by The American Society of Hematology.
PY - 2020/2/25
Y1 - 2020/2/25
N2 - Various grading systems are currently used for chimeric antigen receptor (CAR) T-cell-related toxicity, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS).We compared the recently proposed American Society for Transplantation and Cellular Therapy (ASTCT) grading system to other grading scores in 2 populations of adults: Patients (n = 53) with B-cell acute lymphoblastic leukemia (B-ALL) treated with 1928z CAR T-cells (clinicaltrials.gov #NCT01044069), and patients (n = 49) with diffuse large B-cell lymphoma (DLBCL) treated with axicabtagene-ciloleucel (axi-cel) or tisagenlecleucel after US Food and DrugAdministration approval. According to ASTCT grading, 82%of patients had CRS, 87% in the B-ALL and 77% in the DLBCL groups (axi-cel: 86%, tisagenlecleucel: 54%), whereas 50% of patients experienced ICANS, 55% in the B-ALL and 45% in the DLBCL groups (axi-cel: 55%, tisagenlecleucel: 15%). All grading systems agreed on CRS and ICANS diagnosis in 99% and 91%of cases, respectively. However,when analyzed grade by grade, only 25%and 54%of patients had the same grade in each system for CRS and ICANS, respectively, as different systems score symptoms differently (upgrading or downgrading their severity), leading to inconsistent final grades. Investigation of possible management implications in DLBCL patients showed that different recommendations on tocilizumab and steroids across current guidelines potentially result in either overtreating or delaying treatment. Moreover, because these guidelines are based on single products and different grading systems, they cannot be universally applied. To avoid discrepancies in assessing and managing toxicities of different products,we propose that unified grading be used across clinical trials and in practice and that paired management guidelines with product-specific indications be developed.
AB - Various grading systems are currently used for chimeric antigen receptor (CAR) T-cell-related toxicity, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS).We compared the recently proposed American Society for Transplantation and Cellular Therapy (ASTCT) grading system to other grading scores in 2 populations of adults: Patients (n = 53) with B-cell acute lymphoblastic leukemia (B-ALL) treated with 1928z CAR T-cells (clinicaltrials.gov #NCT01044069), and patients (n = 49) with diffuse large B-cell lymphoma (DLBCL) treated with axicabtagene-ciloleucel (axi-cel) or tisagenlecleucel after US Food and DrugAdministration approval. According to ASTCT grading, 82%of patients had CRS, 87% in the B-ALL and 77% in the DLBCL groups (axi-cel: 86%, tisagenlecleucel: 54%), whereas 50% of patients experienced ICANS, 55% in the B-ALL and 45% in the DLBCL groups (axi-cel: 55%, tisagenlecleucel: 15%). All grading systems agreed on CRS and ICANS diagnosis in 99% and 91%of cases, respectively. However,when analyzed grade by grade, only 25%and 54%of patients had the same grade in each system for CRS and ICANS, respectively, as different systems score symptoms differently (upgrading or downgrading their severity), leading to inconsistent final grades. Investigation of possible management implications in DLBCL patients showed that different recommendations on tocilizumab and steroids across current guidelines potentially result in either overtreating or delaying treatment. Moreover, because these guidelines are based on single products and different grading systems, they cannot be universally applied. To avoid discrepancies in assessing and managing toxicities of different products,we propose that unified grading be used across clinical trials and in practice and that paired management guidelines with product-specific indications be developed.
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U2 - 10.1182/bloodadvances.2019000952
DO - 10.1182/bloodadvances.2019000952
M3 - Article
C2 - 32084260
AN - SCOPUS:85082179456
SN - 2473-9529
VL - 4
SP - 676
EP - 686
JO - Blood Advances
JF - Blood Advances
IS - 4
ER -