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

• DOI: 10.1007/s40262-016-0477-1
• Publication Date: 2016-11-28T20:45:32Z
• Authors: Pamela L. Clemens; Xiaoyu Yan; Henk M. Lokhorst; Sagar Lonial; Nedjad Losic; Imran Khan; Richard Jansson; Tahamtan Ahmadi; Kristen Lantz; Honghui Zhou; Thomas Puchalski; Xu Steven Xu
• Keywords: Daratumumab; Regimen

Daratumumab is a CD38 monoclonal antibody recently approved for the treatment of multiple myeloma (MM). We report daratumumab pharmacokinetic data from GEN501, phase I/II dose-escalation (0.005–24 mg/kg) and dose-expansion (8 or 16 study, SIRIUS, II study mg/kg), in relapsed refractory MM. Noncompartmental analysis was conducted to characterize pharmacokinetics, and, both studies, exhibited nonlinear characteristics. Decreasing clearance with increasing dose suggests saturation target-mediated at higher levels, whereas decreasing over time repeated dosing may be due tumor burden reductions as CD38-positive cells are eliminated. These other analyses support use recommended regimen (16 mg/kg weekly 8 weeks, every 2 weeks 4 thereafter) rapidly saturate during maintain when weeks.