Considering the relevance of understanding the mechanism by which BTK inhibition impairs immune response, we sought to determine the effects of ibrutinib and acalabrutinib on the macrophage/monocyte population in CLL during a fungal infection by A. fumigatus. We demonstrate that BTK inhibition upon exposure to ibrutinib and acalabrutinib significantly hampered the inflammatory response of NLC during A. fumigatus infection. The gene discussed is BTK; the disease is B-cell chronic lymphocytic leukemia.