Comparing CAR T-cell toxicity grading systems: application of the ASTCT grading system and implications for management

被引:114
作者
Pennisi, Martina [1 ,2 ,3 ]
Jain, Tania [1 ]
Santomasso, Bianca D. [4 ,5 ]
Mead, Elena [5 ,6 ]
Wudhikarn, Kitsada [7 ,8 ]
Silverberg, Mari Lynne [1 ]
Batlevi, Yakup [1 ]
Shouval, Roni [1 ]
Devlin, Sean M. [9 ]
Batlevi, Connie [5 ,10 ]
Brentjens, Renier J. [5 ,11 ]
Dahi, Parastoo B. [1 ,5 ]
Diamonte, Claudia [11 ]
Giralt, Sergio [1 ,5 ]
Halton, Elizabeth F. [11 ]
Maloy, Molly [1 ]
Palomba, Maria Lia [5 ,10 ]
Sanchez-Escamilla, Miriam [1 ,12 ]
Sauter, Craig S. [1 ,5 ]
Scordo, Michael [1 ,5 ]
Shah, Gunjan [1 ,5 ]
Park, Jae H. [5 ,11 ]
Perales, Miguel-Angel [1 ,5 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplant Serv, 1275 York Ave,Box 298, New York, NY 10065 USA
[2] Univ Milan, Dept Oncol & Hematooncol, Milan, Italy
[3] Fdn IRCCS Inst Nazl Tumori, Dept Oncol & Hematooncol, Div Hematol, Milan, Italy
[4] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA
[5] Weill Cornell Med Coll, Dept Med, New York, NY USA
[6] Mem Sloan Kettering Canc Ctr, Dept Anesthesiol & Crit Care Med &, New York, NY 10065 USA
[7] Mem Sloan Kettering Canc Ctr, Parker Inst Canc Immunotherapy, New York, NY 10065 USA
[8] Chulalongkorn Univ, Dept Med, Div Hematol & Res, Unit Translat Hematol, Bangkok, Thailand
[9] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA
[10] Mem Sloan Kettering Canc Ctr, Lymphoma Serv, Dept Med, New York, NY 10065 USA
[11] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10065 USA
[12] Res Inst Marques Valdecilla, Dept Hematol Malignancies & Stem Cell Transplanta, Santander, Spain
基金
美国国家卫生研究院;
关键词
THERAPY;
D O I
10.1182/bloodadvances.2019000952
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 Drug Administration 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.
引用
收藏
页码:676 / 686
页数:11
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