title: Blood concentrations of alemtuzumab and antiglobulin responses in patients with chronic lymphocytic leukemia following intravenous or subcutaneous routes of administration.
abstract: Alemtuzumab is a humanized anti-CD52 antibody licensed for refractory B-cell chronic lymphocytic leukemia (B-CLL), when given intravenously at 30 mg thrice weekly. However, the intravenous route is associated with infusion-related reactions and is inconvenient. We measured blood concentrations in 30 relapsed patients treated with intravenous alemtuzumab and in 20 patients from a previously untreated group who received similar doses subcutaneously. Highest trough samples in the intravenous group were less than 0.5 microg/mL to 18.3 microg/mL (mean 5.4 microg/mL). The cumulative dose required to reach 1.0 microg/mL was 13 mg to 316 mg (mean 90 mg). Higher blood concentrations correlated with the achievement of better clinical responses and minimal residual disease. The highest measured concentrations in the subcutaneous group were similar (0.6 microg/mL to 24.8 microg/mL, mean 5.4 microg/mL). However, the cumulative dose to reach 1.0 microg/mL was higher: 146 mg to 1106 mg (mean 551 mg). No antiglobulin responses were detected in 30 patients given intravenous alemtuzumab whereas 2 of 32 patients given subcutaneous alemtuzumab made substantial anti-idiotype responses. Thus, subcutaneous alemtuzumab achieved concentrations similar to those for intravenous alemtuzumab, although with slightly higher cumulative doses. Subcutaneous alemtuzumab is more convenient and better tolerated but may be associated with some patients forming anti-alemtuzumab antibodies, particularly those patients who were previously untreated.
authors.affiliation: Therapeutic Antibody Centre, Old Road, Headington, Oxford, OX3 7JT, United Kingdom. geoff.hale@path.ox.ac.uk
authors.forename: Geoff
authors.initials: G
authors.lastname: Hale
authors.forename: Peppy
authors.initials: P
authors.lastname: Rebello
authors.forename: Lee R
authors.initials: LR
authors.lastname: Brettman
authors.forename: Chris
authors.initials: C
authors.lastname: Fegan
authors.forename: Ben
authors.initials: B
authors.lastname: Kennedy
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.forename: Mike
authors.initials: M
authors.lastname: Leach
authors.forename: Jeanette
authors.initials: J
authors.lastname: Lundin
authors.forename: Håkan
authors.initials: H
authors.lastname: Mellstedt
authors.forename: Paul
authors.initials: P
authors.lastname: Moreton
authors.forename: Andy C
authors.initials: AC
authors.lastname: Rawstron
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
authors.forename: Anders
authors.initials: A
authors.lastname: Osterborg
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
mesh_terms: D000074323:Alemtuzumab; D000906:Antibodies / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood* / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage* / Q000097:blood* / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D016903:Drug Monitoring; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D010599:Pharmacokinetics; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab