Pharmacokinetics of Daratumumab Following Intravenous Infusion in Relapsed or Refractory Multiple Myeloma After Prior Proteasome Inhibitor and Immunomodulatory Drug Treatment

被引:60
作者
Clemens, Pamela L. [1 ]
Yan, Xiaoyu [2 ]
Lokhorst, Henk M. [3 ]
Lonial, Sagar [4 ]
Losic, Nedjad [5 ]
Khan, Imran [2 ]
Jansson, Richard [1 ]
Ahmadi, Tahamtan [1 ]
Lantz, Kristen [1 ]
Zhou, Honghui [1 ]
Puchalski, Thomas [1 ]
Xu, Xu Steven [2 ]
机构
[1] Janssen Res & Dev LLC, 1400 McKean Rd,POB 776, Spring House, PA 19477 USA
[2] Janssen Res & Dev LLC, Raritan, NJ USA
[3] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands
[4] Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, Atlanta, GA 30322 USA
[5] Genmab AS, Copenhagen, Denmark
关键词
STEM-CELL TRANSPLANTATION; MANAGEMENT; MONOTHERAPY; SURVIVAL;
D O I
10.1007/s40262-016-0477-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Daratumumab is a CD38 monoclonal antibody recently approved for the treatment of multiple myeloma (MM). We report daratumumab pharmacokinetic data from GEN501, a phase I/II dose-escalation (0.005-24 mg/kg) and dose-expansion (8 or 16 mg/kg) study, and SIRIUS, a phase II study (8 or 16 mg/kg), in relapsed or refractory MM. Noncompartmental analysis was conducted to characterize daratumumab pharmacokinetics, and, in both studies, daratumumab exhibited nonlinear pharmacokinetic characteristics. Decreasing daratumumab clearance with increasing dose suggests saturation of target-mediated clearance at higher dose levels, whereas decreasing clearance over time with repeated dosing may be due to tumor burden reductions as CD38-positive cells are eliminated. These and other pharmacokinetic data analyses support the use of the recommended dose regimen of daratumumab (16 mg/kg weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4 weeks thereafter) to rapidly saturate target-mediated clearance during weekly dosing and maintain saturation when dosing every 2 or 4 weeks.
引用
收藏
页码:915 / 924
页数:10
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