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- Title
Pharmacokinetics of Daratumumab Following Intravenous Infusion in Relapsed or Refractory Multiple Myeloma After Prior Proteasome Inhibitor and Immunomodulatory Drug Treatment.
- Authors
Clemens, Pamela; Yan, Xiaoyu; Lokhorst, Henk; Lonial, Sagar; Losic, Nedjad; Khan, Imran; Jansson, Richard; Ahmadi, Tahamtan; Lantz, Kristen; Zhou, Honghui; Puchalski, Thomas; Xu, Xu; Clemens, Pamela L; Lokhorst, Henk M; Xu, Xu Steven
- Abstract
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.
- Subjects
PHARMACOKINETICS; INTRAVENOUS therapy; MONOCLONAL antibodies; CANCER relapse; MULTIPLE myeloma treatment; PROTEASOME inhibitors; IMMUNOLOGICAL adjuvants; THERAPEUTICS
- Publication
Clinical Pharmacokinetics, 2017, Vol 56, Issue 8, p915
- ISSN
0312-5963
- Publication type
journal article
- DOI
10.1007/s40262-016-0477-1