Review of the Clinical Pharmacokinetics and Pharmacodynamics of Alemtuzumab and Its Use in Kidney Transplantation

Alemtuzumab is a humanized monoclonal antibody against CD52 and causes depletion of T and B lymphocytes, monocytes, and NK cells. Alemtuzumab is registered for the treatment of multiple sclerosis (MS) and is also used in chronic lymphocytic leukemia (CLL). Alemtuzumab is used off-label in kidney transplantation as induction and anti-rejection therapy. The objective of this review is to present a review of the pharmacokinetics, pharmacodynamics, and use of alemtuzumab in kidney transplantation. A systematic literature search was conducted using Ovid Medline, Embase, and Cochrane Central Register of controlled trials. No pharmacokinetic or dose-finding studies of alemtuzumab have been performed in kidney transplantation. Although such studies were conducted in patients with CLL and MS, these findings cannot be directly extrapolated to transplant recipients, because CLL patients have a much higher load of CD52-positive cells and, therefore, target-mediated clearance will differ between these two indications. Alemtuzumab used as induction therapy in kidney transplantation results in a lower incidence of acute rejection compared to basiliximab therapy and comparable results as compared with rabbit anti-thymocyte globulin (rATG). Alemtuzumab used as anti-rejection therapy results in a comparable graft survival rate compared with rATG, although infusion-related side effects appear to be less. There is a need for pharmacokinetic and dose-finding studies of alemtuzumab in kidney transplant recipients to establish the optimal balance between efficacy and toxicity. Furthermore, randomized controlled trials with sufficient follow-up are necessary to provide further evidence for the treatment of severe kidney transplant rejection.