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

Daniel W. Lee, Bianca D. Santomasso, Frederick L. Locke, Armin Ghobadi, Cameron J. Turtle, Jennifer N. Brudno, Marcela V. Maus, Jae H. Park, Elena Mead, Steven Pavletic, William Y. Go, Lamis Eldjerou, Rebecca A. Gardner, Noelle Frey, Kevin J. Curran, Karl Peggs, Marcelo Pasquini, John F. DiPersio, Marcel R.M. van den Brink, Krishna V KomanduriStephan A. Grupp, Sattva S. Neelapu

Research output: Contribution to journalReview article

79 Citations (Scopus)

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 of patients up to age 25 years 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 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.

Original languageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StatePublished - Jan 1 2019

Fingerprint

Neurotoxicity Syndromes
Nervous System
Antigen Receptors
Transplantation
Bone Marrow
Cytokines
Cell- and Tissue-Based Therapy
Clinical Trials
B-Cell Lymphoma
Hematologic Neoplasms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunotherapy
Neoplasms
B-Lymphocytes
Therapeutics
Safety
Antibodies

Keywords

  • CAR T cell therapy
  • Cellular immunotherapy
  • Consensus grading
  • Cytokine release syndrome
  • Immune effector cell
  • Neurotoxicity

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

ASBMT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. / Lee, Daniel W.; Santomasso, Bianca D.; Locke, Frederick L.; Ghobadi, Armin; Turtle, Cameron J.; Brudno, Jennifer N.; Maus, Marcela V.; Park, Jae H.; Mead, Elena; Pavletic, Steven; Go, William Y.; Eldjerou, Lamis; Gardner, Rebecca A.; Frey, Noelle; Curran, Kevin J.; Peggs, Karl; Pasquini, Marcelo; DiPersio, John F.; van den Brink, Marcel R.M.; Komanduri, Krishna V; Grupp, Stephan A.; Neelapu, Sattva S.

In: Biology of Blood and Marrow Transplantation, 01.01.2019.

Research output: Contribution to journalReview article

Lee, DW, Santomasso, BD, Locke, FL, Ghobadi, A, Turtle, CJ, Brudno, JN, Maus, MV, Park, JH, Mead, E, Pavletic, S, Go, WY, Eldjerou, L, Gardner, RA, Frey, N, Curran, KJ, Peggs, K, Pasquini, M, DiPersio, JF, van den Brink, MRM, Komanduri, KV, Grupp, SA & Neelapu, SS 2019, 'ASBMT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells', Biology of Blood and Marrow Transplantation. https://doi.org/10.1016/j.bbmt.2018.12.758
Lee, Daniel W. ; Santomasso, Bianca D. ; Locke, Frederick L. ; Ghobadi, Armin ; Turtle, Cameron J. ; Brudno, Jennifer N. ; Maus, Marcela V. ; Park, Jae H. ; Mead, Elena ; Pavletic, Steven ; Go, William Y. ; Eldjerou, Lamis ; Gardner, Rebecca A. ; Frey, Noelle ; Curran, Kevin J. ; Peggs, Karl ; Pasquini, Marcelo ; DiPersio, John F. ; van den Brink, Marcel R.M. ; Komanduri, Krishna V ; Grupp, Stephan A. ; Neelapu, Sattva S. / ASBMT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. In: Biology of Blood and Marrow Transplantation. 2019.
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AU - Go, William Y.

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AU - Peggs, Karl

AU - Pasquini, Marcelo

AU - DiPersio, John F.

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N2 - 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 of patients up to age 25 years 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 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.

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