Joint modelling and simulation of M-protein dynamics and progression-free survival for alternative isatuximab dosing with pomalidomide/dexamethasone.

Aims: Addition of isatuximab (Isa) to pomalidomide/dexamethasone (Pd) significantly improved progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (RRMM). We aimed to characterize the relationship between serum M-protein kinetics and PFS in the phase 3 ICARIA-MM trial (NCT02990338), and to evaluate an alternative dosing regimen of Isa by simulation.

Methods: Data from the ICARIA-MM trial comparing Isa 10 mg/kg weekly for 4 weeks then every 2 weeks (QW-Q2W) in combination with Pd versus Pd in 256 evaluable RRMM patients were used.

A novel method based on unbiased correlations tests for covariate selection in nonlinear mixed effects models: The COSSAC approach.

Building a covariate model is a crucial task in population pharmacokinetics and pharmacodynamics in order to understand the determinants of the interindividual variability. Identifying a good covariate model usually requires many runs. Several procedures have been proposed in the past to automatize this task.

Efficient Pharmacokinetic Modeling Workflow With the MonolixSuite: A Case Study of Remifentanil.

MonolixSuite is a software widely used for model-based drug development. It contains interconnected applications for data visualization, noncompartmental analysis, nonlinear mixed effect modeling, and clinical trial simulations. Its main assets are ease of use via an interactive graphical interface, computation speed, and efficient parameter estimation even for complex models.