Daratumumab for treatment-refractory antibody-mediated diseases in neurology.
CIDP
autoimmune encephalitis
daratumumab
myasthenia gravis
sporadic late onset nemaline myopathy
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
13
01
2022
received:
19
11
2021
accepted:
27
01
2022
pubmed:
1
2
2022
medline:
10
5
2022
entrez:
31
1
2022
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Substances chimiques
Antibodies, Monoclonal
0
Autoantibodies
0
daratumumab
4Z63YK6E0E
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1847-1854Informations de copyright
© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
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