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

COLADO A; FERNANDEZ GRECCO H; GAMBERALE R; BALBOA L; GIORNADO, M; SASIAIN MC; JANCIC C; CABREJO, M; BEZARES F; MARÍN FRANCO JL; BLEJER J; GRASSI BASSINO A; GENOULA M; CORDINI G; VERGARA RUBIO M; ELIAS E; RISNIK D; BORGE M

Mar del Plata

Congreso; Reunión Anual de la Sociedad Argentina de Inmunología; 2018

Sociedad Argentina de Inmunología

Ibrutinib is a first-in-class Btk inhibitor used in the treatment of Chronic Lymphocytic Leukemia (CLL). Besides its effects on leukemic B-cells, ibrutinib also affects functions on T cells, NK cells and macrophages.Second generation Btk-inhibitors with higher selectivity have been developed and are being evaluated in clinical trials. Here we aimed to evaluate the effect of second-generation Btk inhibitors, spebrutinib and acalabrutinib, on macrophages´ phenotype and functions.Macrophages were differentiated by culturing human monocytes with M-CSF. For M1 polarization GM-CSF+IFN-ɣ was used. Phagocytosis of CFSE labeled rituximab-coated CLL cells and M1/M2-associated markers were evaluated by flow cytometry. Glucose and lactate concentration in culture supernatants was determined using commercial kits and TNF-α secretion by ELISA. Statistical significance was determined using the Friedman test and the Dunn?s post-test.While we confirmed that ibrutinib reduces rituximab-coated CLL cells phagocytosis, we found that spebrutinib and acalabrutinib did not (n=7, p