Understanding the Dose Regimen for Daratumumab in Patients with Relapsed or Refractory Multiple Myeloma (MM) after Prior Proteasome Inhibitors (pis) and Immunomodulatory Drugs (imids): A Quantitative Pharmacologic Perspective

Introduction: Daratumumab is a first-in-class human anti-CD38 immunoglobulin G1 (IgG1) monoclonal antibody in clinical development for multiple myeloma (MM). Nonlinear concentration- and time-dependent pharmacokinetics was observed due to target-mediated drug disposition. Identification of an optimal dose regimen was complicated by the interactions between daratumumab pharmacokinetics and pharmacodynamics of the target (CD38) and a clinical dosing schedule with decreasing dose frequency over time. The objective of this analysis was to understand and justify the recommended dose and dosing schedule for daratumumab in MM patients from a quantitative pharmacologic perspective.