# Brain-Imaging Markers of Neurotoxicity and Long-Term Outcomes after CAR-T Cell Therapy

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2024 · $676,469

## Abstract

Project Summary
CD19-directed chimeric antigen receptor (CAR)-T cell therapy for relapsed or refractory B-cell acute
lymphoblastic leukemia (ALL) induces complete remission in 70-90% of otherwise incurable patients. CAR-T
cell engagement with their target antigens induces expansion of activated CAR-T cells, producing cytokines
and other pro-inflammatory mediators. Unfortunately, in approximately 50% of patients this inflammatory
response also produces an Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), a serious
neurotoxicity characterized by delirium, encephalopathy, dysphasia, and in severe cases, diffuse cerebral
edema that can be fatal. Additionally, ICANS increases the risk for long-term cognitive impairments; possible
consequences that have not been systematically studied. ICANS therefore remains a major challenge for the
wider adoption of CAR-T cell therapy, creating an urgent need to mitigate or prevent ICANS, to understand its
pathophysiology, and to predict its adverse long-term outcomes. We have compelling preliminary data
demonstrating that several pre-infusion neuroimaging markers predict ICANS with high accuracy. Building
upon these findings, we will develop a predictive algorithm in this proposal that will facilitate closer monitoring
of high-risk patients, support with preventive treatments, and risk-adapted dosing of CAR-T cells. Our
preliminary data also suggest that neuroimaging biomarkers serve as objective surrogates for clinical and
subclinical ICANS. These markers may guide future development of targeted anti-cytokine and small molecule
inhibitor-based interventions to inhibit or block neurotoxicity-specific pathways. Finally, preliminary data support
our hypothesis that ICANS-induced abnormalities in attentional networks of the brain cause long-term
neurocognitive impairments. Adverse outcomes are also seen in low grade neurotoxicity, suggesting a greater
need than previously anticipated for cognitive and behavioral interventions in CAR-T cell patients, rather than
only in patients with florid neurotoxicity. Expanding on our pilot study, we propose to conduct a prospective,
longitudinal cohort study of 80 consecutive patients who receive CAR-T cell therapy for B-ALL. We will collect
state-of-the-art (a) clinical assessments for ICANS and CRS, (b) multi-modal MRI to characterize brain
structure, function, and metabolism, (c) peripheral blood samples for immunophenotyping using CyTOF (mass
Cytometry by Time-Of-Flight) and to profile cytokines and biomarkers of blood brain barrier integrity, and (d)
neurocognitive testing to characterize cognitive changes. Longitudinal data will be collected at (1) a pre-
infusion baseline; and then post-infusion on (2) Day 10, when the ICANS risk is greatest, (3) Day 28, upon
ICANS resolution, and (4) month 12, for long-term outcomes. These data will identify, with unparalleled
inferential capacity, brain-based predictors and inflammatory mediators of ICANS, help develop brain...

## Key facts

- **NIH application ID:** 10816563
- **Project number:** 5R01CA274137-02
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Ravi Bansal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $676,469
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10816563

## Citation

> US National Institutes of Health, RePORTER application 10816563, Brain-Imaging Markers of Neurotoxicity and Long-Term Outcomes after CAR-T Cell Therapy (5R01CA274137-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10816563. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*