Daratumumab treatment for therapy-refractory anti-CASPR2 encephalitis

J Neurol. 2020 Feb;267(2):317-323. doi: 10.1007/s00415-019-09585-6. Epub 2019 Oct 19.


The anti-CD38 antibody daratumumab is approved for treatment of refractory multiple myeloma and acts by depletion of plasma cells and modification of various T-cell functions. Its safety, immunological effects and therapeutic potential was evaluated in a 60-year old patient with life-threatening and treatment-refractory anti-CASPR2 encephalitis requiring medical care and artificial ventilation in an intensive care unit. His autoimmune dysfunction was driven by exceptional high anti-CASPR2 autoantibody titers combined with an abnormally increased T-cell activation. As he remained unresponsive to standard and escalation immunotherapies (methylprednisolone, plasma exchange, immunoadsorption, immunoglobulins, rituximab and bortezomib), therapy was escalated to 13 cycles of 16 mg/kg daratumumab. During the treatment period, clinical, radiological, histological and laboratory findings, including quantification of autoreactive and protective antibody levels and FACS-based immune phenotyping, were analyzed. Daratumumab treatment was associated with significant clinical improvement, substantial reduction of anti-CASPR2 antibody titers, especially in CSF, decrease of immunoglobulin levels and protective vaccine titers, as well as normalization of initially increased T-cell activation markers. However, the patient died of Gram-negative septicemia in a neurorehabilitation center. In conclusion, our findings suggest that daratumumab induces not only depletion of autoreactive long-lived plasma cells associated with improvements of neurological sequelae, but also severe side effects requiring clinical studies investigating efficacy and safety of anti-CD38 therapy in antibody-driven autoimmune encephalitis.

Keywords: Anti-CASPR2 encephalitis; Autoimmune encephalitis; Critical care; Daratumumab.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacology*
  • Autoimmune Diseases of the Nervous System / drug therapy*
  • Autoimmune Diseases of the Nervous System / immunology
  • Encephalitis / drug therapy*
  • Encephalitis / immunology
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / pharmacology*
  • Male
  • Membrane Proteins / immunology*
  • Middle Aged
  • Nerve Tissue Proteins / immunology*


  • Antibodies, Monoclonal
  • CNTNAP2 protein, human
  • Immunologic Factors
  • Membrane Proteins
  • Nerve Tissue Proteins
  • daratumumab