Associations of ofatumumab exposure and treatment outcomes in patients with untreated CLL receiving chemoimmunotherapy

Abstract

Relationships between patient characteristics, ofatumumab pharmacokinetics, and treatment outcomes were investigated in this phase 2 trial of ofatumumab plus fludarabine and cyclophosphamide (FC) in untreated chronic lymphocytic leukemia. Patients were randomized 1:1 to receive 500 or 1000 mg ofatumumab (Cycle 1; 300 mg) plus FC every 4 weeks for six cycles. Median C_max and C_trough values were similar at Cycle 1 regardless of the ultimate clinical outcome. At later doses, these values were higher for patients with complete response (CR) than for other patients. Higher C_max and C_trough values at Cycles 3 and 6 were significantly associated with an increased likelihood of CR, whereas ofatumumab pharmacokinetics were not associated with an objective response (OR) on the basis of univariate analyses. Multivariate analyses indicated that baseline patient/disease factors were predominantly associated with CR (17p status) or OR (bulky lymphadenopathy, gender, and serum thymidine kinase), rather than ofatumumab pharmacokinetics. Trial registration: www.clinicaltrials.gov (NCT00410163).

Keywords:

• Chemoimmunotherapy
• chronic lymphocytic leukemia
• ofatumumab
• pharmacokinetics

Acknowledgements

The authors would like to thank the patients and the following investigators who participated in the study:

Czech Republic: T. Kozak, J. Mayer, L. Smolej, M. Trneny; Germany: U. Dührsen, J. Dürig, G. Hess, N. Schmitz, S. Stilgenbauer; Lithuania: L. Griskevicius; United Kingdom: G.A. Follows, P. Hillmen; United States: S. Gregory, F.J. Hernandez-Ilizaliturri, T.J. Kipps, S. Padmanabhan, L.C. Pinter-Brown, W.G. Wierda.

The authors would also like to thank the following Independent Data Monitoring Committee members: H. Hagberg, Professor in Oncology, Uppsala University, Uppsala, Sweden (Chairman); and P. Johnson, Professor in Oncology, Southampton General Hospital, Southampton, UK.

This study was supported by Genmab and GlaxoSmithKline.

We thank T. Paul, PhD, of Paul Medical Writing, Inc., Raleigh, NC, USA, for writing and editorial assistance and PharmaWrite, LLC, Princeton, NJ, USA, for preparing the final figures (medical writing services and figure preparation were funded by GlaxoSmithKline). Articulate Science, Manchester, UK is also thanked for editorial assistance (formatting for publication funded by Novartis Pharmaceuticals).

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.1080/10428194.2016.1195497.