Pharmacokinetics and pharmacokinetic/pharmacodynamic associations of ofatumumab, a human monoclonal CD20 antibody, in patients with relapsed or refractory chronic lymphocytic leukemia: a phase 1-2 study

Bertrand Coiffier (1) , Nedjad Losic (2) , Birgitte Billmann Rönn (3) , Stéphane Leprêtre (4) , Lars Möller Pedersen , Ole Gadeberg (5) , Henrik Frederiksen (6) , Marinus H.J. van Oers (7) , James Wooldridge , Janusz Kloczko (8) , Jerzy Holowiecki (9) , Andrzej Hellmann (10) , Jan Walewski (11) , Tadeusz Robak (12) , Jörgen Pedersen (3)

1 Service d'Hematologie
2 Biometrics
3 Pharcometrics
4 HEMATOLOGIE
5 Haematology
6 Hematology
7 Hematology
8 Hematology
9 Haematology and Bone Marrow Transplantation
10 Hematology
11 Hematology
12 Department of Hematology

The purpose of this phase 1-2 study was to investigate the association between pharmacokinetic (PK) properties of ofatumumab, a human monoclonal CD20 antibody, and outcomes in 33 patients with relapsed/refractory chronic lymphocytic leukemia 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 tumor burden. The trial was registered at www.clinicaltrials.gov (NCT00093314).

Mots clés: Medicine

Bertrand Coiffier, Nedjad Losic, Birgitte Billmann Rönn, Stéphane Leprêtre, Lars Möller Pedersen, et al.. Pharmacokinetics and pharmacokinetic/pharmacodynamic associations of ofatumumab, a human monoclonal CD20 antibody, in patients with relapsed or refractory chronic lymphocytic leukemia: a phase 1-2 study. British Journal of Haematology, 2010, ⟨10.1111/j.1365-2141.2010.08193.x⟩. ⟨hal-00552592⟩