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




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Clinical Pharmacokinetics

, Volume 56, Issue 8, pp 915–924

First Online: 29 November 2016

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.

Electronic supplementary materialThe online version of this article doi:10.1007-s40262-016-0477-1 contains supplementary material, which is available to authorized users.

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Autor: Pamela L. Clemens - Xiaoyu Yan - Henk M. Lokhorst - Sagar Lonial - Nedjad Losic - Imran Khan - Richard Jansson - Tahamtan

Fuente: https://link.springer.com/



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