Griffith University

Author Of 2 Presentations

Imaging Late Breaking Abstracts

LB1177 - PAMRINO: International MRI and clinical data repository for neuromyelitis optica spectrum disorder (ID 469)

Abstract

Background

Neuromyelitis optica spectrum disorders (NMOSD) encompasses a group of rare inflammatory diseases which primarily target the optic nerves, spinal cord, and brain. Typically, magnetic resonance imaging (MRI) data from single-center studies comprise 20-50 patients, limiting statistical power for outcomes research. Using retrospective data from the PArallel MRI in NmOsd (PAMRINO) study, a novel prospective NMOSD image repository (NMOsDIR) representing multiple international sites was coordinated by Charité-Universitätsmedizin Berlin and the Medical Image Analysis Center (Basel).

Objectives

The PAMRINO study aimed to investigate and analyze retrospective MRIs collected from NMOSD-specialized centers, potentially for the evaluation of disease-related brain and spinal cord changes. NMOsDIR serves as an international imaging research resource (comprising standardized retinal optical coherence tomography and MRI scans) and clinical data hub for prospective studies in NMOSD. Linking imaging and clinical data, as well as enabling analysis pipelines for each modality, will facilitate multi-centered studies using sufficient data and statistical power to advance outcomes research in this rare disease.

Methods

For clinical data collection in PAMRINO, a Research Electronic Data Capture (REDCap) platform was used, where participating centers entered data relevant for NMOSD patient monitoring. An image database (XNAT) was established for image uploads. This large collection of MRI data is currently being analyzed in a joint international effort of NMOSD clinical neuroradiologists and scientists.

Results

Brain, spinal cord, and optic nerve MRI scans with associated clinical data were collected from 514 NMOSD patients and 56 healthy controls from 17 international centers. Roughly 20,000 individual MRI scans from patients and healthy controls were collected. Of these, 78% had T1-weighted cerebral MRIs (55% with 3D scans), 80% had T2-weighted cerebral MRIs (54% with 3D scans), 86% had T2-weighted spinal cord MRIs (55% with 3D scans), and 35% had optic nerve MRIs.

Conclusions

We successfully established PAMRINO, an international collaborative retrospective MRI and clinical data repository. The knowledge gained during this process provided important new insights, where the initial analysis of the dataset has underscored the large degree of heterogeneity in image and clinical data collection in NMOSD-specialized centers. Thus, calling for more standardized methods of data acquisition and imaging analysis, as not to limit research opportunities. The new longitudinal, prospective NMOsDIR will help us to answer many pressing - yet open - questions regarding patients seropositive for aquaporin-4-IgG+, myelin oligodendrocyte glycoprotein-IgG+ and other autoimmune-related diseases. In turn, such a strategy will strengthen future capabilities in research, diagnosis, monitoring and improving NMOSD patient care.

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Clinical Trials Poster Presentation

P0226 - Phase I study of ATA188, an off-the-shelf, allogeneic Epstein-Barr virus-targeted T-cell immunotherapy for progressive forms of multiple sclerosis (ID 1635)

Speakers
Presentation Number
P0226
Presentation Topic
Clinical Trials

Abstract

Background

Epstein-Barr virus (EBV) is a necessary risk factor for the development of multiple sclerosis (MS) [Abrahamyan S et al. JNNP 2020; Pakpoor J et al. Mult Scler 2012]. Early experience with autologous EBV-specific T-cell adoptive immunotherapy proved safe and may offer clinical benefit [Pender MP et al. JCI Insight 2018].

Objectives

This Phase I study evaluated the safety and potential efficacy of off-the-shelf, allogeneic EBV-targeted T-cell therapy (ATA188) in adults with progressive forms of MS (NCT03283826).

Methods

In part 1, four cohorts received escalating doses of ATA188 to determine the recommended part 2 dose (RP2D). Patients (pts) were followed for 1-year and given the option to participate in a 4-year open label extension (OLE) at the RP2D (cohort 3 dose). In addition to safety, sustained disability improvement (SDI) was assessed, defined as improvement in Expanded Disability Status Scale (EDSS) or Timed 25-Foot Walk (T25FW) at ≥2 consecutive time points [Pender MP et al. EAN 2020; LB130]. Other measures evaluated include Fatigue Severity Scale (FSS), 12-item MS Walking Scale (MSWS-12), MS Impact Scale-29 (physical; MSIS-29), and whole brain volume (via magnetic resonance imaging [MRI]). As of August 2020, we expect 12-month (m) data for all 4 cohorts, which marks the end of the dose finding portion of this study, will be available for presentation.

Results

As of April 2020, 25 pts had received ≥1 dose of ATA188. No grade >3 events, dose-limiting toxicities, cytokine release syndrome, graft vs host disease, or infusion reactions were observed. Two treatment-emergent serious adverse events were reported: muscle spasticity (grade 2; not treatment related) and MS relapse (grade 3; possibly treatment related). Efficacy endpoints were assessed in cohorts 1–4 (n=24) at 6m and in cohorts 1–3 (n=17) at 12m. Six pts met SDI criteria at 6m and 5 pts met it at 12m, which was driven by EDSS in all but 2 pts at both 6 and 12m. At both timepoints, a higher proportion of pts showed SDI with increasing dose. In cohorts 1–3, all pts with SDI at 6m maintained it through 12m. Pts with SDI (vs those without) tended to have greater improvements in FSS, MSWS-12, and MSIS-29 (physical) scores, as well as less reduction in whole brain volume on MRI, from baseline to 12m. As of June 2020, OLE data from the 15m timepoint were available for 4 pts; 3 had SDI at 6m and 12m which was maintained at 15m.

Conclusions

Preliminary data indicate ATA188 is well tolerated. A higher proportion of pts showed sustained disability improvement (SDI) with increasing dose. Pts who achieved SDI at any timepoint maintained it at all future timepoints and tended to show improvements in fatigue, physical function, and MRI whole brain volume at 12m. Based on these data, part 2 of the study (randomized placebo-controlled portion) has been initiated using the cohort 3 dose.

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