title: Relationship between pharmacokinetic profile of subcutaneously administered alemtuzumab and clinical response in patients with chronic lymphocytic leukemia.
abstract: Alemtuzumab serum levels and clinical response after subcutaneous administration (10 mg 3 times/week for six weeks) have been explored in 29 chronic lymphocytic leukemia patients receiving the monoclonal antibody as consolidation. Serum concentrations after each administration gradually increased during the first week and more markedly during weeks 2 and 3, approaching the steady-state at week 6. Absorption continued slowly through the tissues for about 2-3 weeks after the last administration, starting to decrease thereafter. Difference between Responders and Non-responders was statistically significant: maximal concentration (Cmax) was 1.69 μg/mL vs. 0.44 μg/mL; concentration before subcutaneous administration (Cpre-dose) on day 15 was 0.7 vs. 0.21 μg/mL, area under curve (AUC0-12h) was 11.09 vs. 2.26 μgxh/mL for Responders and Non-responders, respectively. Higher systemic exposure to alemtuzumab correlated with a better clinical response and minimal residual disease. Results suggest that an adjusted schedule according to serum level could improve clinical outcome of patients receiving subcutaneous alemtuzumab.
authors.affiliation: Foundation IRCCS Policlinico San Matteo, Laboratory of Clinical Pharmacokinetics, P.le Golgi 2, 27100 Pavia, Italy. m.montagna@smatteo.pv.it
authors.forename: Michela
authors.initials: M
authors.lastname: Montagna
authors.forename: Marco
authors.initials: M
authors.lastname: Montillo
authors.forename: Maria A
authors.initials: MA
authors.lastname: Avanzini
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tedeschi
authors.forename: Livia
authors.initials: L
authors.lastname: Visai
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricci
authors.forename: Eleonora
authors.initials: E
authors.lastname: Vismara
authors.forename: Enrica
authors.initials: E
authors.lastname: Morra
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
mesh_terms: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000097:blood / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D007700:Kinetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy*; D018655:Lymphocyte Count; D008875:Middle Aged; D018365:Neoplasm, Residual; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab