[Pubmed] Daratumumab for treatment-refractory antibody-mediated diseases in neurology

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Eur J Neurol. 2022 Jan 31. doi: 10.1111/ene.15266. Online ahead of print.

ABSTRACT

BACKGROUND: A fraction of patients with antibody-mediated autoimmune diseases remain unresponsive to first/second-line and sometimes even to escalation immunotherapies. Since 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 4 (range 4-9) immunotherapies were treated with 4-20 cycles of 16mg/kg daratumumab.

RESULTS: Daratumumab allowed a substantial clinical improvement in all patients, as measured by modified Rankin Scale (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; CSF 58%, n=5) and vaccine-induced titers for rubella (50%) and tetanus toxoid (74%). Treatment-related toxicities grade 3 or higher occurred in 5 patients, including one death.

CONCLUSION: 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.

PMID:35098616 | DOI:10.1111/ene.15266


Source: https://pubmed.ncbi.nlm.nih.gov/3509861 ... 0&v=2.17.5