Journal Article

DZNE-2022-00252

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Daratumumab for treatment-refractory antibody-mediated diseases in neurology.

Scheibe, F.Extern* ; Ostendorf, L. ; Prüss, H.DZNE* ; Radbruch, H. ; Aschman, T. ; Hoffmann, S. ; Blau, I.-W. ; Meisel, C. ; Alexander, T. ; Meisel, A.

2022
Blackwell Science Oxford

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Please use a persistent id in citations: doi:10.1111/ene.15266

Abstract: A fraction of patients with antibody-mediated autoimmune diseases remain unresponsive to first-/second-line and sometimes even to escalation immunotherapies. Because these patients are still affected by poor outcome and increased mortality, we investigated the safety and efficacy of the plasma cell-depleting anti-CD38 antibody daratumumab in life-threatening, antibody-mediated autoimmune diseases.In this retrospective, single-center case series, seven patients with autoantibody-driven neurological autoimmune diseases (autoimmune encephalitis, n = 5; neurofascin antibody-associated chronic inflammatory demyelinating polyneuropathy associated with sporadic late onset nemaline myopathy, n = 1; seronegative myasthenia gravis, n = 1) unresponsive to a median of four (range = 4-9) immunotherapies were treated with four to 20 cycles of 16 mg/kg daratumumab.Daratumumab allowed a substantial clinical improvement in all patients, as measured by modified Rankin Scale (mRS; before treatment: mRS =5, n = 7; after treatment: median mRS =4, range = 0-5), Clinical Assessment Scale in Autoimmune Encephalitis (from median 21 to 3 points, n = 5), Inflammatory Neuropathy Cause and Treatment disability score (from 7 to 0 points, n = 1), and Quantitative Myasthenia Gravis score (from 16 to 8 points, n = 1). Daratumumab induced a substantial reduction of disease-specific autoreactive antibodies, total IgG (serum, 66%, n = 7; cerebrospinal fluid, 58%, n = 5), and vaccine-induced titers for rubella (50%) and tetanus toxoid (74%). Treatment-related toxicities Grade 3 or higher occurred in five patients, including one death.Our findings suggest that daratumumab provided a clinically relevant depletion of autoreactive long-lived plasma cells, identifying plasma cell-targeted therapies as promising escalation therapy for highly active, otherwise treatment-refractory autoantibody-mediated neurological diseases.

Keyword(s): Antibodies, Monoclonal (MeSH) ; Autoantibodies (MeSH) ; Encephalitis (MeSH) ; Hashimoto Disease (MeSH) ; Humans (MeSH) ; Myasthenia Gravis (MeSH) ; Nervous System Diseases: drug therapy (MeSH) ; Neurology (MeSH) ; Retrospective Studies (MeSH) ; CIDP ; autoimmune encephalitis ; daratumumab ; myasthenia gravis ; sporadic late onset nemaline myopathy

Note: ISSN 1468-1331 not unique: **2 hits**. (CC BY-NC-ND)

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Contributing Institute(s):

1. Autoimmune Enzephalopathies (AG Prüß)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2022

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Database coverage:
; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection

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