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

Martina Pennisi, Tania Jain, Bianca D. Santomasso, Elena Mead, Kitsada Wudhikarn, Mari Lynne Silverberg, Yakup Batlevi, Roni Shouval, Sean M. Devlin, Connie Batlevi, Renier J. Brentjens, Parastoo B. Dahi, Claudia Diamonte, Sergio Giralt, Elizabeth F. Halton, Molly Maloy, Maria Lia Palomba, Miriam Sanchez-Escamilla, Craig S. Sauter, Michael ScordoGunjan Shah, Jae H. Park, Miguel Angel Perales

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)676-686
Number of pages11
JournalBlood advances
Volume4
Issue number4
DOIs
StatePublished - 25 Feb 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 by The American Society of Hematology.

Funding

This work was supported by National Institutes of Health (NIH), National Cancer Institute Cancer Center Support Grant P30CA008748. M.P. was supported by an American-Italian Cancer Foundation PostDoctoral Research Fellowship and by Associazione italiana contro le leucemie-linfomi e mieloma Milano e Provincia ONLUS. M.S.-E. was supported by a Research Institute of Marques de Valdecilla Wenceslao-Lopez-Albo grant (WLA17/03).

FundersFunder number
Associazione italiana contro le leucemie-linfomi e mieloma Milano e Provincia ONLUS
National Cancer Institute Cancer Center Support
Research Institute of Marques de Valdecilla Wenceslao-Lopez-AlboWLA17/03
National Institutes of Health
National Cancer InstituteP30CA008748
American-Italian Cancer Foundation

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