ID #989 Neurosurgical management for GD2 CAR T-cells Therapy in Pediatric and Young Adults Brain Tumors
Giada Del Baldo, Matteo Amicucci, Francesca Del Bufalo, Franco Locatelli, Angela Mastronuzzi, Andrea CaraiAbstract
Background
Availability of fresh tumor tissue is a pre-requisite before considering GD2 CAR T treatment for patients with central nervous system tumors. Moreover, CAR T-cell therapy for central nervous system (CNS) tumors carries a relevant risk of neurotoxicity, particularly tumor inflammation–associated neurotoxicity (TIAN). We describe a monoinstitutional experience on the neurosurgical management of children and young adults treated by GD2 CAR T-cells for brain tumors.
Methods
Consecutive patients with relapsed/refractory CNS tumors receiving intravenous GD2-directed CAR T-cells were included in the study. Surgical biopsy was performed before treatment whenever tumoral GD2 expression was not previously available. Post-treatment biopsy was proposed in selected cases. All patients were implanted with a ventricular access device connected to a telemetric intracranical pressure (ICP) monitoring device.
Results
Twenty patients were included in the study. Diagnoses included embryonal tumors (n = 10), high-grade glioma (HGG; n = 4), diffuse midline glioma (DMG; n = 4), and ependymoma (n = 2). Pre-treatment biopsy was required in 10/20 patients. Post-operative biopsy was performed in 3 cases. Baseline median ICP was 6.3 cmH2O (range −5.8 to 37.4), with a median peak of 16.8 cmH2O (range 6.74–41). Median ICP variation was 11.5 points (range 5.4–30) at a median time of day 10. ICP increased after CAR-T infusion in all patients, occurring concomitantly with cytokine release syndrome. Elevations were significantly higher in patients with HGG and DMG, the only tumor types associated with TIAN. ICP changes were not correlated with severity of toxicity, but ICP did correlate with peak CAR T-cell expansion in peripheral blood and cerebrospinal fluid. No patient required an urgent invasive procedure.
Conclusions
neurosurgical management supports patients receiving CAR T-cells. ICP telemonitoring during GD2 CAR T-cell therapy is feasible and clinically useful. A delayed ICP peak around day 10 highlights a key monitoring window. This non-invasive approach improves safety and reduces invasive procedures.