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.
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.
Coiffier
Bertrand
B
Département d'Hématologie, Centre Hospitalier Lyon Sud, Pierre-Benite Cedex, France. bertrand coiffier@chu-lyon.fr
Losic
Nedjad
N
Rønn
Birgitte Biilmann
BB
Lepretre
Stéphane
S
Pedersen
Lars Møller
LM
Gadeberg
Ole
O
Frederiksen
Henrik
H
van Oers
Marinus H J
MH
Wooldridge
James
J
Kloczko
Janusz
J
Holowiecki
Jerzy
J
Hellmann
Andrzej
A
Walewski
Jan
J
Robak
Tadeusz
T
Petersen
Jørgen
J
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; D000970:Antineoplastic Agents; C527517:ofatumumab