Haematology 2018

Ibrutininb Mechanism of action

Interactions between the tumour microenvironment and malignant B cells play an important role in B-cell homing, adhesion and migration through activation of intracellular pathways in the B cells. 1,2 BTK’s pivotal role in signalling through B-cell surface receptors results in activation of pathways necessary for B- cell trafficking, chemotaxis and adhesion. 3

Through irreversible inhibition of BTK, ibrutinib is believed to disrupt key malignant processes and: 3,4

• Induce apoptosis • Inhibit adhesion (may lead to lymphocytosis) • Inhibit migration and homing (prevents malignant cells from homing back to lymph organs)

Chemical structure of ibrutinib 4

1. de Gorter DJJ, et al. Immunity 2007;26:93-104. 2. Burger JA, et al. Blood 2009;114:3367-3375. 3. Buggy J et al. Int Rev Immunol 2012; 31:119-132. 4. Chavez J, et al. Core Evid 2013; 8:37-45.