Effect of the Bruton Tyrosine Kinase (Btk)-inhibitors spebrutinib (CC-292) and acalabrutinib (ACP-196) on macrophage´s phenotype and functions.

Buenos Aires

Congreso; 3er Congreso Iberoamericano de Leucemia Linfocítica Crónica 2018 (IBAM 2018); 2018

Ibrutinib is a first-in-class Btk inhibitor used in the treatment of CLL. Besides its effects on leukemic B-cells, ibrutinib also affects functions on T cells, NK cells and macrophages. While some of these effects might be explained by inhibition of Btk, ibrutinib also inhibits other off-target kinases. Second generation Btk-inhibitors have been developed and are being evaluated in clinical trials. Here we aimed to evaluate the effect of second-generation Btk inhibitors, spebrutinib (CC-292/AVL-292) and acalabrutinib (ACP-196), on macrophages´ phenotype and functions.While we confirmed that ibrutinib reduces rituximab-coated CLL cells phagocytosis, we found that spebrutinib and acalabrutinib did not affect phagocytosis (n=7, p