In this article, we will discuss Blinatumomab (Mechanism of Action). So, let’s get started.
Mechanism of Action
Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. It activates endogenous T cells by connecting CD3 in the T-cell receptor (TCR) complex with CD19 on benign and malignant B cells. Blinatumomab mediates the formation of a synapse between the T-cell and the tumor cell, upregulation of cell adhesion molecules, production of cytolytic proteins, release of inflammatory cytokines, and proliferation of T cells, which result in redirected lysis of CD19+ cells.
Pharmacodynamics
During the continuous intravenous infusion over 4 weeks, the pharmacodynamic response was characterized by T-cell activation and initial redistribution, reduction in peripheral B cells, and transient cytokine elevation. Peripheral T-cell redistribution (ie, T-cell adhesion to blood vessel endothelium and/or transmigration into tissue) occurred after start of Blinatumomab infusion or dose escalation. T-cell counts initially declined within 1 to 2 days and then returned to baseline levels within 7 to 14 days in the majority of patients. Increase of T-cell counts above baseline (T-cell expansion) was observed in few patients. Peripheral B cell counts decreased to less than or equal to 10 cells/microliter during the first treatment cycle at doses >5 mcg/m²/day or >9 mcg/day in the majority of patients. No recovery of peripheral B-cell counts was observed during the 2-week Blinatumomab-free period between treatment cycles. Incomplete depletion of B cells occurred at doses of 0.5 mcg/m2/day and 1.5 mcg/m2/day and in a few patients at higher doses. Cytokines including IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-alpha, and IFN-gamma were measured, and IL-6, IL-10, and IFN-gamma were elevated. The highest elevation of cytokines was observed in the first 2 days following start of Blinatumomab infusion. The elevated cytokine levels returned to baseline within 24 to 48 hours during the infusion. In subsequent treatment cycles, cytokine elevation occurred in fewer patients with lesser intensity compared to the initial 48 hours of the first treatment cycle.