Neurotoxicity-Associated Brain FDG-PET Alterations Following BCMA CAR T-Cell Therapy in Multiple Myeloma

This exploratory study investigated alterations in cerebral metabolism and metabolic connectivity using 18 F-fluorodeoxyglucose positron emission tomography (F-18 FDG-PET) in patients with multiple myeloma with neurotoxicity after B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy.

The retrospective study included 20 BCMA CAR T-cell therapy recipients who underwent brain F-18 FDG-PET imaging (15 with baseline PET scans). Brain metabolism was quantified using standardized uptake value ratios (SUVRs), with the cerebellum as the reference region. Metabolic connectivity was assessed using correlation matrices and network topology metrics. Metabolic patterns were age-adjusted and compared between patients with and without neurotoxicity.

Neurotoxicity occurred in 7 patients. SUVR analysis involving those with neurotoxicity demonstrated significantly reduced post-treatment FDG uptake in the left precentral gyrus and striatum. Greater declines were observed in FDG uptake within the left inferior occipital cortex and striatum in patients with neurotoxicity than in those without. Metabolic connectivity analysis identified 508 significantly altered regional pairs, primarily with reduced frontotemporal correlations. Hub node analysis demonstrated a redistribution of network centrality from higher-order cortical regions to temporal and occipital areas, with reduced centrality in the insular and limbic regions among patients with neurotoxicity.

Patients with neurotoxicity after BCMA CAR T-cell therapy demonstrated distinct metabolic-level and network-level differences on F-18 FDG-PET, highlighting the potential of brain PET imaging to elucidate the underlying mechanisms and warranting further investigation in larger cohorts.