Abstract Details

Title Development of Resistance to B-Cell Depletion Following Ten Years of Effective Rituximab Treatment in a Patient with Neuromyelitis Optica

Topic Autoimmune Neurology

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-008

Objective To present a report of a patient with neuromyelitis optica (NMO) who developed resistance to B-cell depletion following ten years of effective Rituximab treatment.

Background NMO is characterized by potentially neurologically devastating episodes of longitudinally-extensive-transverse-myelitis (LETM) and optic neuritis. Rituximab, a monoclonal antibody targeting CD20+ B-cells, has demonstrated efficacy in preventing NMO relapses. For NMO patients treated with Rituximab, maintenance of B-cell depletion is important, with increased relapse risk upon B-cell reconstitution.

Design/Methods CASE REPORT: A 65-year-old man with NMO presented for continued Rituximab treatment. His initial presentation eleven years prior included optic neuritis, followed later by LETM, after which he was found seropositive for aquaporin-4. He began Rituximab and was maintained on 700mg IV every five months (375mg/m²* 1.86m²), remaining clinically stable with CD19+ cells <1% of lymphocytes throughout ten years of treatment. A decade following Rituximab initiation, CD19+ cells reconstituted and represented 5% of lymphocytes. He received a repeat 700mg treatment, with CD19+ cells still representing 3%. He received two additional doses of 1,000mg two weeks apart, with B-cells remaining between 2% - 4%. No anti-drug antibodies to Rituximab were detected and adequate drug levels were demonstrated. He remained clinically stable throughout the one year since B-cell reconstitution.

Results We illustrate the case of an NMO patient who had undergone Rituximab treatment for over ten years and developed eventual resistance to B-cell depletion. While B-cell re-emergence is concerning for potential relapses, he has remained relapse-free since reconstitution.

Conclusions Although B-cell therapy has gained favor for the treatment of several neuroimmunological conditions such as NMO and multiple sclerosis, the long term effects of decades of chronic treatment are unknown. Delayed resistance to B-cell depletion has not been previously reported but may grow more frequent as chronic use of B-cell therapies becomes more commonplace. The mechanisms by which resistance might occur will be discussed.

Authors/Disclosures
Asaff Harel, MD PRESENTER	Dr. Harel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Harel has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Harel has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Expert Institute.
	No disclosure on file
	No disclosure on file
Souhel Najjar, MD (Hofstra University North Shore LIJ School of Medicine Lennox Hill Hospital)	Dr. Najjar has nothing to disclose.

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