title: Pharmacokinetics and pharmacokinetic/pharmacodynamic associations of ofatumumab, a human monoclonal CD20 antibody, in patients with relapsed or refractory chronic lymphocytic leukaemia: a phase 1-2 study.
abstract: The purpose of this phase 1-2 study was to investigate the association between the pharmacokinetic properties of ofatumumab, a human monoclonal CD20 antibody, and outcomes in 33 patients with relapsed/refractory chronic lymphocytic leukaemia receiving 4 weekly infusions of ofatumumab. The ofatumumab concentration profiles were fitted well by a two-compartment model with different elimination rate constant at first infusion compared to the remaining infusions in line with the observed rapid and sustained B-cell depletion. Exposure to ofatumumab was linked to clinical outcomes: high exposure was associated with higher probability of overall clinical response and longer progression-free survival. This association still remained statistically significant even when adjusting for relevant baseline covariates including tumour burden.
authors.affiliation: Département d'Hématologie, Centre Hospitalier Lyon Sud, Pierre-Benite Cedex, France. bertrand coiffier@chu-lyon.fr
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
authors.forename: Nedjad
authors.initials: N
authors.lastname: Losic
authors.forename: Birgitte Biilmann
authors.initials: BB
authors.lastname: Rønn
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lepretre
authors.forename: Lars Møller
authors.initials: LM
authors.lastname: Pedersen
authors.forename: Ole
authors.initials: O
authors.lastname: Gadeberg
authors.forename: Henrik
authors.initials: H
authors.lastname: Frederiksen
authors.forename: Marinus H J
authors.initials: MH
authors.lastname: van Oers
authors.forename: James
authors.initials: J
authors.lastname: Wooldridge
authors.forename: Janusz
authors.initials: J
authors.lastname: Kloczko
authors.forename: Jerzy
authors.initials: J
authors.lastname: Holowiecki
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.forename: Jan
authors.initials: J
authors.lastname: Walewski
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Jørgen
authors.initials: J
authors.lastname: Petersen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20 / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; D000970:Antineoplastic Agents; C527517:ofatumumab