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 articlepeer-review

743 Scopus citations

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

ASJC Scopus subject areas

  • Oncology

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