Chimeric antigen receptor T-cell therapy-assessment and management of toxicities

Sattva S. Neelapu, Sudhakar Tummala, Partow Kebriaei, William Wierda, Cristina Gutierrez, Frederick L. Locke, Krishna V Komanduri, Yi Lin, Nitin Jain, Naval Daver, Jason Westin, Alison M. Gulbis, Monica E. Loghin, John F. De Groot, Sherry Adkins, Suzanne E. Davis, Katayoun Rezvani, Patrick Hwu, Elizabeth J. Shpall

Research output: Contribution to journalReview article

270 Citations (Scopus)

Abstract

Immunotherapy using T-cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH). Neurotoxicity, termed CAR-T-cell-related encephalopathy syndrome (CRES), is the second most-common adverse event, and can occur concurrently with or after CRS. Intensive monitoring and prompt management of toxicities is essential to minimize the morbidity and mortality associated with this potentially curative therapeutic approach; however, algorithms for accurate and consistent grading and management of the toxicities are lacking. To address this unmet need, we formed a CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising investigators from multiple institutions and medical disciplines who have experience in treating patients with various CAR-T-cell therapy products. Herein, we describe the multidisciplinary approach adopted at our institutions, and provide recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy.

Original languageEnglish (US)
Pages (from-to)47-62
Number of pages16
JournalNature Reviews Clinical Oncology
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Antigen Receptors
Cell- and Tissue-Based Therapy
Cytokines
Hemophagocytic Lymphohistiocytosis
Brain Diseases
T-Cell Antigen Receptor
Immunotherapy
Research Personnel
Morbidity
T-Lymphocytes
Mortality
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Oncology

Cite this

Neelapu, S. S., Tummala, S., Kebriaei, P., Wierda, W., Gutierrez, C., Locke, F. L., ... Shpall, E. J. (2018). Chimeric antigen receptor T-cell therapy-assessment and management of toxicities. Nature Reviews Clinical Oncology, 15(1), 47-62. https://doi.org/10.1038/nrclinonc.2017.148

Chimeric antigen receptor T-cell therapy-assessment and management of toxicities. / Neelapu, Sattva S.; Tummala, Sudhakar; Kebriaei, Partow; Wierda, William; Gutierrez, Cristina; Locke, Frederick L.; Komanduri, Krishna V; Lin, Yi; Jain, Nitin; Daver, Naval; Westin, Jason; Gulbis, Alison M.; Loghin, Monica E.; De Groot, John F.; Adkins, Sherry; Davis, Suzanne E.; Rezvani, Katayoun; Hwu, Patrick; Shpall, Elizabeth J.

In: Nature Reviews Clinical Oncology, Vol. 15, No. 1, 01.01.2018, p. 47-62.

Research output: Contribution to journalReview article

Neelapu, SS, Tummala, S, Kebriaei, P, Wierda, W, Gutierrez, C, Locke, FL, Komanduri, KV, Lin, Y, Jain, N, Daver, N, Westin, J, Gulbis, AM, Loghin, ME, De Groot, JF, Adkins, S, Davis, SE, Rezvani, K, Hwu, P & Shpall, EJ 2018, 'Chimeric antigen receptor T-cell therapy-assessment and management of toxicities', Nature Reviews Clinical Oncology, vol. 15, no. 1, pp. 47-62. https://doi.org/10.1038/nrclinonc.2017.148
Neelapu, Sattva S. ; Tummala, Sudhakar ; Kebriaei, Partow ; Wierda, William ; Gutierrez, Cristina ; Locke, Frederick L. ; Komanduri, Krishna V ; Lin, Yi ; Jain, Nitin ; Daver, Naval ; Westin, Jason ; Gulbis, Alison M. ; Loghin, Monica E. ; De Groot, John F. ; Adkins, Sherry ; Davis, Suzanne E. ; Rezvani, Katayoun ; Hwu, Patrick ; Shpall, Elizabeth J. / Chimeric antigen receptor T-cell therapy-assessment and management of toxicities. In: Nature Reviews Clinical Oncology. 2018 ; Vol. 15, No. 1. pp. 47-62.
@article{1df09997b22a4ad4be217930fa108603,
title = "Chimeric antigen receptor T-cell therapy-assessment and management of toxicities",
abstract = "Immunotherapy using T-cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH). Neurotoxicity, termed CAR-T-cell-related encephalopathy syndrome (CRES), is the second most-common adverse event, and can occur concurrently with or after CRS. Intensive monitoring and prompt management of toxicities is essential to minimize the morbidity and mortality associated with this potentially curative therapeutic approach; however, algorithms for accurate and consistent grading and management of the toxicities are lacking. To address this unmet need, we formed a CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising investigators from multiple institutions and medical disciplines who have experience in treating patients with various CAR-T-cell therapy products. Herein, we describe the multidisciplinary approach adopted at our institutions, and provide recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy.",
author = "Neelapu, {Sattva S.} and Sudhakar Tummala and Partow Kebriaei and William Wierda and Cristina Gutierrez and Locke, {Frederick L.} and Komanduri, {Krishna V} and Yi Lin and Nitin Jain and Naval Daver and Jason Westin and Gulbis, {Alison M.} and Loghin, {Monica E.} and {De Groot}, {John F.} and Sherry Adkins and Davis, {Suzanne E.} and Katayoun Rezvani and Patrick Hwu and Shpall, {Elizabeth J.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1038/nrclinonc.2017.148",
language = "English (US)",
volume = "15",
pages = "47--62",
journal = "Nature Reviews Clinical Oncology",
issn = "1759-4774",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Chimeric antigen receptor T-cell therapy-assessment and management of toxicities

AU - Neelapu, Sattva S.

AU - Tummala, Sudhakar

AU - Kebriaei, Partow

AU - Wierda, William

AU - Gutierrez, Cristina

AU - Locke, Frederick L.

AU - Komanduri, Krishna V

AU - Lin, Yi

AU - Jain, Nitin

AU - Daver, Naval

AU - Westin, Jason

AU - Gulbis, Alison M.

AU - Loghin, Monica E.

AU - De Groot, John F.

AU - Adkins, Sherry

AU - Davis, Suzanne E.

AU - Rezvani, Katayoun

AU - Hwu, Patrick

AU - Shpall, Elizabeth J.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Immunotherapy using T-cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH). Neurotoxicity, termed CAR-T-cell-related encephalopathy syndrome (CRES), is the second most-common adverse event, and can occur concurrently with or after CRS. Intensive monitoring and prompt management of toxicities is essential to minimize the morbidity and mortality associated with this potentially curative therapeutic approach; however, algorithms for accurate and consistent grading and management of the toxicities are lacking. To address this unmet need, we formed a CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising investigators from multiple institutions and medical disciplines who have experience in treating patients with various CAR-T-cell therapy products. Herein, we describe the multidisciplinary approach adopted at our institutions, and provide recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy.

AB - Immunotherapy using T-cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH). Neurotoxicity, termed CAR-T-cell-related encephalopathy syndrome (CRES), is the second most-common adverse event, and can occur concurrently with or after CRS. Intensive monitoring and prompt management of toxicities is essential to minimize the morbidity and mortality associated with this potentially curative therapeutic approach; however, algorithms for accurate and consistent grading and management of the toxicities are lacking. To address this unmet need, we formed a CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising investigators from multiple institutions and medical disciplines who have experience in treating patients with various CAR-T-cell therapy products. Herein, we describe the multidisciplinary approach adopted at our institutions, and provide recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy.

UR - http://www.scopus.com/inward/record.url?scp=85038265543&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038265543&partnerID=8YFLogxK

U2 - 10.1038/nrclinonc.2017.148

DO - 10.1038/nrclinonc.2017.148

M3 - Review article

C2 - 28925994

AN - SCOPUS:85038265543

VL - 15

SP - 47

EP - 62

JO - Nature Reviews Clinical Oncology

JF - Nature Reviews Clinical Oncology

SN - 1759-4774

IS - 1

ER -