Introduction: Previous work has indicated that ATA188, an investigational Epstein–Barr virus (EBV)-targeted T-cell immunotherapy, is associated with disability improvement in progressive multiple sclerosis (PMS); however, the relationship with neurodegenerative and tissue integrity markers on magnetic resonance imaging (MRI) remains unclear. Objectives: Investigate the relationship between confirmed disability improvement (CDI, based on the Expanded Disability Status Scale [EDSS]) and longitudinal changes in MRI atrophy measures and normalised magnetisation transfer ratio (nMTR) in patients (pts) with PMS treated with ATA188. Methods: This retrospective analysis included pts with PMS treated with ATA188 in part 1 of EMBOLD, the open-label, single-arm Phase I portion, with an open-label extension (OLE). T1-weighted, FLAIR, and nMTR images were analysed between treatment onset and last available follow-up during the OLE (average follow-up 24.9±8.8 months). Percentage brain volume change (PBVC), percentage ventricular volume change (PVVC), and thalamic volume change (TVC) were assessed on T1-weighted MRI. nMTR evolution was measured within baseline unenhancing T2 lesions. Results: 9/24 pts treated with ATA188 achieved sustained disability improvement (SDI) in the initial 12-month period or in the OLE; in 7/9, SDI was driven by EDSS (CDI). As of the most recent data provided, 5/5 pts with CDI remaining in the OLE maintained improvement for a median of 23.5 (range, 16.4–24.7) months. Safety in the OLE was consistent with previous reports. At 12 months, pts achieving SDI (vs not) during the study had significantly less enlargement of ventricular volume (PVVC; p=0.019) but similar PBVC and TVC. Similar trends were observed in pts achieving CDI (vs not). Longitudinal MRI analyses including OLE data showed that pts achieving CDI (vs not) had significantly higher nMTR over time (β=0.14, p=0.005), suggesting increased myelin density. Further, PBVC in pts achieving CDI (vs not) showed less decrease over time (β=0.34,p=0.037) and there was a trend for less ventricular volume enlargement over time (PVVC); TVC did not differ by CDI status. Conclusion: Pts achieving CDI continuing in the OLE sustained CDI for up to 39 months. CDI was associated with less severe brain atrophy at 12 months and increasing nMTR in chronic T2 lesions over time, suggesting that brain structural changes, potentially including remyelination, persist over time and may underlie the CDI associated with ATA188.