Open AccessPopulation Pharmacokinetics of Obinutuzumab (GA101) in Chronic Lymphocytic Leukemia (CLL) and Non‐Hodgkin's Lymphoma and Exposure–Response in CLL
Author(s) -
Gibiansky E,
Gibiansky L,
Carlile D J,
Jamois C,
Buchheit V,
Frey N
Publication year - 2014
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1038/psp.2014.42
Subject(s) - obinutuzumab , chronic lymphocytic leukemia , medicine , oncology , population , pharmacodynamics , lymphoma , pharmacokinetics , leukemia , clinical trial , rituximab , environmental health
Treatment regimens involving obinutuzumab (GA101) demonstrated increased efficacy to rituximab in clinical trials for non‐Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). However, the pharmacokinetic (PK) properties and the exposure–response relationships of obinutuzumab still need to be fully described. Data from four clinical trials of obinutuzumab were analyzed to describe the PK properties in patients with NHL or CLL and the pharmacodynamic (PD) properties in patients with CLL. A population PK model with linear time‐dependent clearance described the obinutuzumab concentration–time course. Diagnosis, baseline tumor size (BSIZ), body weight, and gender were the main covariates affecting obinutuzumab exposure. In patients with CLL, exposure was not associated with safety but showed positive trends of correlation with efficacy. Although efficacy correlated positively with exposure, since both efficacy and exposure correlated negatively with BSIZ, it was not possible to determine with certainty whether it would be beneficial to adjust the dose according to BSIZ. CPT Pharmacometrics Syst. Pharmacol . (2014) 3, e144; doi: 10.1038/psp.2014.42 ; published online 29 October 2014