Pharmacokinetics of alemtuzumab and the relevance in clinical practice.
Alemtuzumab is a humanised monoclonal antibody directed against the CD52 antigen. It is approved for the treatment of B-cell chronic lymphocytic leukemia (CLL) as a monotherapy and is being investigated as combination therapy and consolidation therapy for CLL, as well as in conditioning regimens for stem cell transplantation. The pharmacokinetics (PK) of alemtuzumab is best described by a two-compartment model with large interpatient variability in all PK parameters. Analyses of small patient cohorts suggest that higher serum alemtuzumab levels are associated with better treatment responses. Several patient-specific factors, such as disease status, tumor burden and soluble CD52 levels, appear to influence serum alemtuzumab level. Future studies are needed to improve the PK model of alemtuzumab and to explore a PK-guided dosing schedule, with the goal of maximising the therapeutic benefit of this agent.
Elter
Thomas
T
Department of Internal Medicine, University of Cologne, Cologne, Germany. thomas.elter@uk-koeln.de
Molnar
Istvan
I
Kuhlmann
Jens
J
Hallek
Michael
M
Wendtner
Clemens
C
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000097:blood / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology; D000074301:CD52 Antigen; D006023:Glycoproteins / Q000032:analysis / Q000276:immunology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D010599:Pharmacokinetics; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab