Second generation BTK inhibitors impair the anti‐fungal response of macrophages and neutrophils

COLADO, ANA; MARÍN FRANCO, JOSÉ L.; ELÍAS, ESTEBAN E.; AMONDARAIN, MIKELE; VERGARA RUBIO, MARICEF; SARAPURA MARTÍNEZ, VALERIA; CORDINI, GREGORIO; FUENTES, FEDERICO; BALBOA, LUCIANA; FERNANDEZ GRECCO, HORACIO; PAVLOVSKY, MIGUEL; BEZARES, FERNANDO; MORANDE, PABLO; GIORDANO, MIRTA; GAMBERALE, ROMINA; BORGE, MERCEDES

AMERICAN JOURNAL OF HEMATOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2020 vol. 95

0361-8609

Small-molecule inhibitors targeting the Bruton Tyrosine Kinase (BTKi) havechanged the treatment paradigm for chronic lymphocytic leukemia (CLL) andother B-cell malignancies. Ibrutinib is a first in-class BTKi approved for CLLtreatment and although it shows impressive clinical efficacy in different riskgroups, most patients do not achieve complete responses and requirecontinuous administration. Infections rates during ibrutinib treatment are similaror lower compared to other treatments, but they are still one of the mostfrequent adverse events leading to drug-discontinuation especially inrelapsed/refractory patients (1). The emergence of invasive fungal infections insome treated patients, including cases of invasive aspergillosis with centralnervous system involvement, suggests that ibrutinib may disturb immunologicalmechanisms implicated in fungal defense (2). In line with these clinicalobservations, substantial evidence showed that ibrutinib affects functions onmacrophages and neutrophils (3-6), both critical players for antimicrobialimmune response.