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Review
. 2019 Apr;25(4):625-638.
doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.

ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells

Daniel W Lee  1 , Bianca D Santomasso  2 , Frederick L Locke  3 , Armin Ghobadi  4 , Cameron J Turtle  5 , Jennifer N Brudno  6 , Marcela V Maus  7 , Jae H Park  8 , Elena Mead  9 , Steven Pavletic  6 , William Y Go  10 , Lamis Eldjerou  11 , Rebecca A Gardner  12 , Noelle Frey  13 , Kevin J Curran  14 , Karl Peggs  15 , Marcelo Pasquini  16 , John F DiPersio  4 , Marcel R M van den Brink  8 , Krishna V Komanduri  17 , Stephan A Grupp  18 , Sattva S Neelapu  19
Affiliations
Review

ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells

Daniel W Lee et al. Biol Blood Marrow Transplant. 2019 Apr.

Abstract

Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging as one of the most promising therapies for hematologic malignancies. Two CAR T products were recently approved in the United States and Europe for the treatment ofpatients up to age 25years with relapsed or refractory B cell acute lymphoblastic leukemia and/or adults with large B cell lymphoma. Many more CAR T products, as well as other immunotherapies, including various immune cell- and bi-specific antibody-based approaches that function by activation of immune effector cells, are in clinical development for both hematologic and solid tumor malignancies. These therapies are associated with unique toxicities of cytokine release syndrome (CRS) and neurologic toxicity. The assessment and grading of these toxicities vary considerably across clinical trials and across institutions, making it difficult to compare the safety of different products and hindering the ability to develop optimal strategies for management of these toxicities. Moreover, some aspects of these grading systems can be challenging to implement across centers. Therefore, in an effort to harmonize the definitions and grading systems for CRS and neurotoxicity, experts from all aspects of the field met on June 20 and 21, 2018, at a meeting supported by the American Society for Transplantation and Cellular Therapy (ASTCT; formerly American Society for Blood and Marrow Transplantation, ASBMT) in Arlington, VA. Here we report the consensus recommendations of that group and propose new definitions and grading for CRS and neurotoxicity that are objective, easy to apply, and ultimately more accurately categorize the severity of these toxicities. The goal is to provide a uniform consensus grading system for CRS and neurotoxicity associated with immune effector cell therapies, for use across clinical trials and in the postapproval clinical setting.

Keywords: CAR T cell therapy; Cellular immunotherapy; Consensus grading; Cytokine release syndrome; Immune effector cell; Neurotoxicity.

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Conflict of interest statement

Conflicts of Interest Disclosures

DWL has received clinical trial support from Kite/Gilead and serves as a consultant and advisory board member for Juno Therapeutics/Celgene. BDS has consulted or participated in advisory boards for Juno Therapeutics/Celgene, Kite Pharma/Gilead, and Novartis. FLL has served as a scientific advisor to Kite Pharma and Novartis, and as a consultant to Cellular BioMedicine Group Inc. AG has received research support from Kite Pharma and has served as a scientific advisor and speaker for Kite Pharma. CJT has received research support from Juno Therapeutics and Nektar Therapeutics; has consulted or participated in advisory boards for Juno Therapeutics/Celgene, Nektar Therapeutics, Precision Biosciences, Eureka Therapeutics, Aptevo, Gilead, and Caribou Biosciences; and has option grants in Precision Biosciences, Eureka Therapeutics, and Caribou Biosciences. MVM has received research support from Novartis, Kite, Servier, TCR2, Agentus, and CRISPR Therapeutics; has participated in consulting or advisory boards for Agentus, Bluebird Bio, Cellectis, Juno, Kite, Novartis, Precision Biosciences, Takeda, TCR2. JHP has received research support from Juno Therapeutics, Genentech and Amgen; has consulted or participated in advisory boards for Novartis, Kite, Juno Therapeutics, Shire, Amgen, Pfizer, Takeda, Adaptive Biotechnologies, TG Therapeutics, AstraZeneca and Bayer. JNB, EM, SP, KP, and JFD have no conflicts of interest to report. WYG is employed by Kite, a Gilead Company, and has equity ownership in Gilead Sciences, Inc. LE is employed by Novartis Pharmaceuticals. RAG has participated in advisory boards for Novartis. NF has consulted or participated in advisory boards for Novartis and Servier. KJC has received research support from Juno Therapeutics; has consulted or participated in advisory boards for Juno Therapeutics and Novartis. MCP has received honoraria from Pfizer and consulting with Medigene. MRMVD has received research support from Seres Therapeutics; has consulted, received honorarium from or participated in advisory boards for Seres Therapeutics, Flagship Ventures, Novartis, Evelo, Jazz Pharmaceuticals, Therakos, Amgen, Merck & Co, Inc., Acute Leukemia Forum (ALF) and DKMS Medical Council (Board); has IP Licensing with Seres Therapeutics and Juno Therapeutics. KVK has received support for site participation in clinical trials from Kite, Adaptimmune, Atara and Juno and has served as ad hoc consultant to Kite/Gilead, Juno/Celgene, Novartis, Atara and Merck. SAG has received research and/or clinical trial support from Novartis, Servier and Kite. Consulting, study steering committees, or scientific advisory boards: Novartis, Adaptimmune, Eureka, TCR2, Juno, GlaxoSmithKline, Cellectis, Vertex, Cure Genetics, and Roche. SSN has received research support from Kite/Gilead, Celgene, Cellectis, Poseida, Merck, Acerta, Karus, and BMS; served as consultant and advisory board member for Kite/Gilead, Celgene, Novartis, Unum Therapeutics, Pfizer, and Merck.

Comment in

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