Neurotoxicity of CAR T-cell therapy: the NEUROCART Study
Research type
Research Study
Full title
Longitudinal Neurocognitive Phenotyping of Chimeric Antigen Receptor (CAR) T-Cell Neurotoxicity
IRAS ID
341573
Contact name
Claire Roddie
Contact email
Sponsor organisation
University College London Hospital Trust
Duration of Study in the UK
0 years, 4 months, 4 days
Research summary
Chimeric Antigen Receptor T-Cell (CAR-T) therapy is a highly effective treatment for blood cancers. CAR-T therapy involves removing a patient’s immune T-cells and modifying them to attack cancerous cells, before infusing these CAR-T cells back into the patient where they can treat the cancer. CAR-T effectively treats several cancers which were previously incurable. However, in up to 50% of patients, CAR-T therapy is associated with toxic inflammatory effects on the brain (neurotoxicity). This neurotoxicity is called Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). ICANS is characterised by deficits in thinking and speaking and, in some cases, may progress to death. ICANS significantly limits the use of CAR-T, particularly because the existing treatments for ICANS reduce the efficacy of CAR T treatment. Despite its importance, ICANS is poorly understood.
The NEUROCART project will employ daily tests of cognition and speech in patients receiving CAR-T therapy, coupled with measurement of markers of inflammation (cytokines) to address several questions, the answers to which are currently unknown: 1) Are there any early markers of ICANS after CAR T infusion that could prompt earlier treatment and improve patient outcomes? 2) Is ICANS a global process affecting the whole brain, or a focal process that targets one specific part of the brain? 3) Does ICANS result in any long-term neurological deficits? and 4) Do any pre-existing risk factors predispose patients to developing ICANS?
Answering these questions will have a significantly beneficial impact on patients by allowing proper pre-treatment risk stratification and earlier identification of deterioration. This could potentially allow earlier and more effective treatment of ICANS. The study will also inform our understanding of ICANS and guide future studies and treatment trials. A better understanding of ICANS will significantly increase the safety of a revolutionary, but toxic, cancer treatment.
REC name
Yorkshire & The Humber - Bradford Leeds Research Ethics Committee
REC reference
24/YH/0158
Date of REC Opinion
23 Jul 2024
REC opinion
Favourable Opinion