ID #935 Neuroimaging beyond TIAN: novel neuroimaging patterns in pediatric patients undergoing intracranial B7-H3-CAR T cell therapy

Introduction

Intracranial B7-H3-CAR T cells are a promising immunotherapy for pediatric patients with high-risk CNS tumors.1 Whereas tumor inflammation-associated neurotoxicity (TIAN) is a known complication of therapy, neuroimaging findings unrelated to tumor and their association with new clinical symptoms are incompletely characterized.2

Methods

We performed a retrospective review of pediatric patients with high-risk CNS tumors treated with intracranial B7-H3-CAR T cells at our institution over the past 3 years. We characterized neuroimaging findings unrelated to tumor and evaluated their association with dose level, clinical symptoms, and temporal evolution.

Results

Twenty-five participants with CNS tumors were treated with intracranial B7-H3-CAR T cells. Ten (40%) developed new neuroimaging findings unrelated to tumor, including basilar cistern/cranial nerve enhancement (n = 6), intraventricular enhancement (n = 5) and ventriculomegaly (n = 2). No significant association between neuroimaging findings and dose level was identified in this cohort. In contrast, there was a significant association between new basilar cistern/cranial nerve enhancement and new cranial nerve palsies (Fisher’s exact test, p < 0.05). One participant, treated on the highest dose level, had basilar cistern/cranial nerve enhancement and subsequently developed a symptomatic brainstem infarct while on study therapy. Follow up imaging was available in 8/10 participants, and improvement/resolution of neuroimaging findings was noted in 7 at a median follow up of 40.5 days. One patient had progressive, symptomatic ventriculomegaly in addition to transient basilar cistern/cranial nerve enhancement and was treated with a ventriculoperitoneal shunt.

Conclusions

Together, these findings demonstrate intracranial B7-H3-CAR T cells can lead to transient, basilar inflammatory meningitis, associated with new cranial nerve palsies. Systematic evaluation of the relationship between neuroimaging findings and clinical symptoms across clinical trials is critical to better characterize these associations and potentially inform risk assessment for future pediatric patients receiving intracranial CAR T cell therapy.

References:

1. Vitanza, Nicholas A., et al. “Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial.” Nature medicine 31.3 (2025): 861-868.

2. Mahdi, Jasia, et al. “Tumor inflammation-associated neurotoxicity.” Nature medicine 29.4 (2023): 803-810.