Lymphocyte Reconstitution Patterns in People with MS Being Treated with Rituximab After Alemtuzumab to Reduce the Frequency of Autoimmune Adverse Events in the RAMBLE Trial
Sofia Jimenez Sanchez1, Simon Broadley2, Sonya Marshall-Gradisnik3, Natalie Eaton-Fitch3
1School of Medicine and Dentistry, Gold Coast Campus, Griffith University QLD, Australia, 2Department of Neurology, Gold Coast University Hospital, Southport QLD, Australia, 3National Centre for Neuroimmunology and Emerging Diseases, Griffith University Southport, QLD, Australia
Objective:
To elucidate the effect of the B-cell agent rituximab on lymphocyte subsets following alemtuzumab therapy in multiple sclerosis (MS).
Background:
The anti-52 monoclonal antibody alemtuzumab is a highly effective therapy for relapsing-remitting MS. The common occurrence of autoimmune adverse events has limited the use of alemtuzumab. The RAMBLE trial aims to assess the effect of rituximab in reducing this risk. This is a preliminary analysis of lymphocyte repopulation.
Design/Methods:
The RAMBLE trial is a multicenter study in which small doses of rituximab/placebo are administered to people receiving alemtuzumab for MS. Participants received rituximab or placebo at a ratio of 2:1, on weeks 10 and 30 of both years one and two. Immunophenotyping studies by flow cytometry are conducted before and after each treatment cycle with alemtuzumab and rituximab to assess the immune reconstitution response.
Results:
To date 16 participants have received at least one dose of rituximab/placebo. B lymphocyte repopulation was slower in the rituximab arm compared to placebo following investigational product administration. Prior to alemtuzumab therapy the mean±SD B cell counts were 0.32±0.23x109/L in the rituximab arm and 0.25±0.18x109/L in the placebo arm. In those receiving rituximab, B cell counts fell from 0.21±0.13x109/L before treatment to 0.03±0.06x109/L after treatment. In those receiving placebo counts continued to rise as would be expected. Rituximab therapy did not show any consistent effect on CD4 and CD8 populations.
Conclusions:
We have demonstrated that administration of rituximab following alemtuzumab slows the rate of B cell repopulation. This trial is ongoing.
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