Daratumumab for treatment-refractory antibody-mediated diseases in neurology.

Abstract

BACKGROUND AND PURPOSE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Franziska Scheibe, Lennard Ostendorf, Harald Prüss, Helena Radbruch, Tom Aschman, Sarah Hoffmann, Igor-Wolfgang Blau, Christian Meisel, Tobias Alexander, Andreas Meisel
• Journal: European journal of neurology (Eur J Neurol) Vol. 29 Issue 6 Pg. 1847-1854 (06 2022) ISSN: 1468-1331 [Electronic] England
• PMID: 35098616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

Chemical References

• Antibodies, Monoclonal
• Autoantibodies
• daratumumab

Topics

• Antibodies, Monoclonal
• Autoantibodies
• Encephalitis
• Hashimoto Disease
• Humans
• Myasthenia Gravis
• Nervous System Diseases (drug therapy)
• Neurology
• Retrospective Studies