Impaired lymphocyte depletion and elevated antidrug antibodies with alemtuzumab in MS patients

Takeaway

  • Alemtuzumab antidrug antibodies (ADAs) (pre-infusion binding ADA titers >15,000 and/or complete neutralization at >10-fold dilution) may be associated with reduced post-infusion lymphocyte depletion in some patients with multiple sclerosis (MS). Monitoring lymphocyte depletion over repeat infusion cycles may be useful in this setting.

Why this matters

  • Alemtuzumab is an anti-CD52 targeted monoclonal antibody used to deplete lymphocytes in people with MS.

  • Although alemtuzumab is a humanized antibody, it is highly immunogenic and generates both binding and neutralizing ADAs in the clinical setting.

  • In pivotal trials, ADAs were only seen in 0.6% of people treated with alemtuzumab for one infusion cycle and believed to be clinically insignificant.

  • However, pre-dose binding and neutralizing ADAs were later shown to become increasingly prevalent following subsequent treatment cycles and may limit the biological and clinical efficacy of repeat treatments in some patients.