Evaluate brain fluorodeoxyglucose positron emission tomography (FDG-PET) as an imaging biomarker of chimeric antigen receptor T-cell therapy (CAR-T) associated movement and neurocognitive treatment-emergent toxicity (MNT).

MNT is an increasingly recognized neurocognitive and hypokinetic movement disorder that develops in patients receiving B-cell maturation antigen (BCMA)-targeting CAR-T for multiple myeloma. Diagnosis is challenging due to phenotypic heterogeneity. Although pre-treatment myeloma burden and post-treatment high absolute lymphocyte count (ALC) are described risk factors, there are no established biomarkers. Prior FDG-PET descriptions of MNT have noted frontal-striatal hypometabolism. 

Twelve MNT cases were identified from a prospectively maintained immune effector cell (IEC) program compliance database (N = 330). Thirty-four neurologically intact cases with high ALC (> 3 × 10⁹/L) and myeloma burden served as a comparison cohort. Pre- and post-treatment full body FDG-PET were processed using an institutional pipeline to generate age-matched Z-scores for brain regions of interest (ROI).

Linear mixed effects models were fit to compare ROI Z-scores pre- and post-treatment. Models included fixed effects of time (pre- vs. post-treatment), ROI, and their interaction, with subject included as a random intercept to account for repeated measures. A second model incorporated group membership and its interactions with time and ROI to examine between-group differences. False discovery rate (FDR) correction was applied for multiple comparisons (α = 0.05).

Model-estimated post-treatment Z-score change from baseline within the MNT group was greatest in the putamen, caudate, and pallidum, all surviving FDR correction (p < 0.05). These effects remained stable and significant when the comparison cohort was incorporated into a combined model. No significant baseline differences in ROI Z-scores were observed between groups.

Brain FDG-PET in MNT cases revealed significantly decreased basal ganglia metabolism post-treatment. This regional hypometabolism is in keeping with clinical presentation, supporting FDG-PET as a potential imaging biomarker. Additional validation is needed to confirm these findings.