Rebecca Ronsley, Michelle Choe, Jason Wright, Kristy Seidel, Amy Lee, Jason Wendler, Colleen Annesley, Michael C Jensen, Julie R Park, Nicholas A Vitanza, Juliane Gust
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引用次数: 0
Abstract
Background: Chimeric antigen receptor (CAR) T cell therapy is a promising treatment for central nervous system (CNS) tumors like diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG). Unlike systemic administration, locoregional CAR T therapy may result in tumor inflammation-associated neurotoxicity (TIAN), which was recently defined. This study retrospectively applies TIAN criteria to patients with DIPG/pontine DMG treated with intraventricular B7-H3 CAR T cells in the BrainChild-03 (BC-03) trial (NCT04185038).
Methods: A retrospective analysis of DIPG/pontine DMG patients treated with locoregional B7-H3 CAR T cells in BC-03 was conducted. Neurological symptoms, headache, fever, hydrocephalus, and inflammatory markers were extracted from case reports and medical records. TIAN was classified as type 1 (mechanical damage) or type 2 (electrophysiologic dysfunction), and symptom patterns, resolution, imaging findings, and management were analyzed.
Results: Among 21 patients (ages 2-22) receiving ≥1 infusion, 16 (76%) met TIAN criteria at least once. TIAN occurred in 49 of 152 infusions (32%), mostly grade 1 (n = 34) or grade 2 (n = 14), with one grade 3 event. Common symptoms included headache with fever (51%) and neurologic changes with headache (31%). In most patients, Type 1 vs Type 2 TIAN could not be defined; however, 1 patient required CSF diversion (type 1 TIAN), and 13 had worsening preexisting deficits (type 2). Median symptom resolution was <24 h (range: 0-33).
Conclusions: TIAN was common within this cohort but mostly low-grade and transient. Refining its classification and understanding its clinical impact will aid safety assessments and trial comparisons for CNS-directed CAR T therapies.
期刊介绍：
Neuro-Oncology Practice focuses on the clinical aspects of the subspecialty for practicing clinicians and healthcare specialists from a variety of disciplines including physicians, nurses, physical/occupational therapists, neuropsychologists, and palliative care specialists, who have focused their careers on clinical patient care and who want to apply the latest treatment advances to their practice. These include: Applying new trial results to improve standards of patient care Translating scientific advances such as tumor molecular profiling and advanced imaging into clinical treatment decision making and personalized brain tumor therapies Raising awareness of basic, translational and clinical research in areas of symptom management, survivorship, neurocognitive function, end of life issues and caregiving
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