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Blinatumomab Trimer Formation

Insights from a Mechanistic PKPD Model on the Implications for Switching from Infusion to Subcutaneous Dosing Regimen in Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma


Abstract

Methods

We constructed a mechanistic PKPD model of Acute Lymphoblastic Leukemia that describes blinatumomab PK in circulation, bone marrow, and periphery, engagement with T-cells and normal and malignant B-cells, and the amount of trimers the drug forms at different dosing regimens.

Results

By simulating various potential subcutaneous dosing regimens, we identify conditions where trimer formation dynamics are similar between constant infusion and subcutaneous dosing when accounting for cell death resulting from the trimer formation.

 

This work was initially presented by Applied BioMath. Applied BioMath was acquired by Certara in December 2023.

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