Abstract Details

Title 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

Topic Multiple Sclerosis

Presentation(s) P12 - Poster Session 12 (11:45 AM-12:45 PM)

Poster/Presentation
Number 1-001

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.

Authors/Disclosures
Sofia Jimenez Sanchez, PhD Student PRESENTER	Miss Jimenez Sanchez has received research support from Multiple Sclerosis Australia .
Simon Broadley, PhD, FRACP (Griffith University School of Medicine)	The institution of Dr. Broadley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. The institution of Dr. Broadley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Broadley has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Broadley has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Broadley has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Broadley has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sage. The institution of Dr. Broadley has received research support from NHMRC. The institution of Dr. Broadley has received research support from ARC. The institution of Dr. Broadley has received research support from GCH Foundation. The institution of Dr. Broadley has received research support from NHMRC.
Sonya M. Marshall-Gradisnik, PhD	Prof. Marshall-Gradisnik has nothing to disclose.
Natalie Eaton-Fitch, PhD	Dr. Eaton-Fitch has nothing to disclose.

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