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
- Authors:
-
- Coiffier, Bertrand ;
- Losic, Nedjad ;
- Rønn, Birgitte Biilmann ;
- Lepretre, Stéphane ;
- Pedersen, Lars Møller ;
- Gadeberg, Ole ;
-
Frederiksen, Henrik
;
Close
0000-0001-8905-0220
Haematology, Department of Clinical Research, Faculty of Health Sciences, SDU - van Oers, Marinus H J ;
- Wooldridge, James ;
- Kloczko, Janusz ;
- Holowiecki, Jerzy ;
- Hellmann, Andrzej ;
- Walewski, Jan ;
- Robak, Tadeusz ;
- Petersen, Jørgen
- DOI:
- 10.1111/j.1365-2141.2010.08193.x
- 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.
- Type:
- Journal article
- Language:
- English
- Published in:
- British Journal of Haematology, 2010, Vol 150, Issue 1, p. 58-71
- Keywords:
- Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, CD20; Antineoplastic Agents; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Models, Biological; Recurrence; Survival Analysis; Treatment Outcome
- Main Research Area:
- Medical science
- Publication Status:
- Published
- Review type:
- Peer Review
- Submission year:
- 2010
- Scientific Level:
- Scientific
- ID:
- 16110324
