EFFECT OF THE BRUTON TYROSINE KINASE (BTK)-INHIBITORS SPEBRUTINIB (CC-292) AND ACALABRUTINIB (ACP-196) ON MACROPHAGE´S PHENOTYPE AND FUNCTIONS

COLADO, ANA; ELÍAS, ESTEBAN E.; GENOULA, MELANIE; BEZARES, FERNANDO R.; JANCIC, CAROLINA; BALBOA, LUCIANA; RISNIK, DENISE; CORDINI, GREGORIO; BLEJER, JOSELINA; CABREJO, MARÍA; GIORDANO, MIRTA; BORGE, MERCEDES; MARÍN FRANCO, JOSÉ LUIS; VERGARA RUBIO, MARICEF; GRASSI BASSINO, ALEJANDRA; FERNANDEZ GRECCO, HORACIO; SASIAIN, MARIA DEL CARMEN; GAMBERALE, ROMINA

Mar del Plata

Congreso; Reunión Conjunta SAIC SAI SAFIS 2018; 2018

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