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Ibrutinib Treatment and Response to Fungal Infection in Patients With CLL

By: Anna Nowogrodzki
Posted: Wednesday, November 11, 2020

The Bruton’s tyrosine kinase inhibitors ibrutinib and acalabrutinib inhibited the inflammatory response of in vitro nurse-like cells from patients with chronic lymphocytic leukemia (CLL), according to recent research. The cells displayed a decrease in the signaling pathways triggered by the fungus Aspergillus fumigatus and decreased phagocytosis and engulfment. Roberto Marasca, MD, of the University of Modena and Reggio Emilia, Italy, and colleagues published their results in Frontiers in Immunology.

“These modifications may compromise an efficient inflammatory response during A fumigatus infection, leading to a possible insurgence of invasive fungal infections,” the authors wrote.

The authors generated nurse-like cells in culture from blood samples from patients with CLL at Modena Hospital in Italy. They treated the nurse-like cells with ibrutinib, acalabrutinib, or vehicle (control) and then incubated them with fungal conidia of A fumigatus. They also isolated peripheral blood mononuclear cells from patients receiving ibrutinib treatment and healthy controls.

In vitro, nurse-like cells treated with ibrutinib displayed decreased inflammatory response to A fumigatus fungal infection compared with control cells. Ibrutinib reduced some signaling pathways associated with response to the fungus. Circulating CD14-positive monocytes isolated from patients with CLL during ibrutinib therapy displayed reduced phagocytosis and tumor necrosis factor-alpha secretion. However, the authors were not able to test cells isolated from patients being treated with acalabrutinib.

“Further work is required to understand why some patients are more prone to fungal infections during treatment to identify who might benefit from prophylaxis and to define factors that add to the risk,” the study authors concluded.

Disclosure: The study authors reported no conflicts of interest.



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