Ibrutinib blocks Btk-dependent NF-ĸB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosis

Amelia Bercusson, Thomas Colley, Anand Shah, Adilia Warris, Darius Armstrong-James

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Ibrutinib is a small molecule Bruton tyrosine kinase (Btk) inhibitor approved by the Food and Drug Administration for clinical use in the treatment of chronic lymphocytic leukemia, Waldenström macroglobulinemia, and as a second-line treatment of lymphoma and chronic graft-versus-host disease.1 An association with pulmonary aspergillosis was observed shortly after Ibrutinib was licensed for use.2 A recent phase Ib study of Ibrutinib treatment of primary central nervous system lymphoma reported a 39% incidence of invasive aspergillosis, in patients concurrently treated with corticosteroids, in the absence of neutropenia.3 Studies of Aspergillus fumigatus infection in Btk−/− mice revealed focal pneumonia and large airway mucous plugs, mirroring findings in macrophage-depleted models of pulmonary aspergillosis.
Original languageEnglish
Pages (from-to)1985-1988
Number of pages4
JournalBlood
Volume132
Issue number18
Early online date18 Jul 2018
DOIs
Publication statusPublished - 1 Nov 2018

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Aspergillus fumigatus
Macrophages
Aspergillus
Phagocytosis
Pulmonary Aspergillosis
Lymphoma
Waldenstrom Macroglobulinemia
Aspergillosis
Neurology
B-Cell Chronic Lymphocytic Leukemia
United States Food and Drug Administration
Grafts
Pneumonia
Adrenal Cortex Hormones
Therapeutics
Central Nervous System
Transplants
Molecules
Incidence
Infection

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Ibrutinib blocks Btk-dependent NF-ĸB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosis. / Bercusson, Amelia; Colley, Thomas; Shah, Anand; Warris, Adilia; Armstrong-James, Darius.

In: Blood, Vol. 132, No. 18, 01.11.2018, p. 1985-1988.

Research output: Contribution to journalArticle

Bercusson, Amelia ; Colley, Thomas ; Shah, Anand ; Warris, Adilia ; Armstrong-James, Darius. / Ibrutinib blocks Btk-dependent NF-ĸB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosis. In: Blood. 2018 ; Vol. 132, No. 18. pp. 1985-1988.
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abstract = "Ibrutinib is a small molecule Bruton tyrosine kinase (Btk) inhibitor approved by the Food and Drug Administration for clinical use in the treatment of chronic lymphocytic leukemia, Waldenstr{\"o}m macroglobulinemia, and as a second-line treatment of lymphoma and chronic graft-versus-host disease.1 An association with pulmonary aspergillosis was observed shortly after Ibrutinib was licensed for use.2 A recent phase Ib study of Ibrutinib treatment of primary central nervous system lymphoma reported a 39{\%} incidence of invasive aspergillosis, in patients concurrently treated with corticosteroids, in the absence of neutropenia.3 Studies of Aspergillus fumigatus infection in Btk−/− mice revealed focal pneumonia and large airway mucous plugs, mirroring findings in macrophage-depleted models of pulmonary aspergillosis.",
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AB - Ibrutinib is a small molecule Bruton tyrosine kinase (Btk) inhibitor approved by the Food and Drug Administration for clinical use in the treatment of chronic lymphocytic leukemia, Waldenström macroglobulinemia, and as a second-line treatment of lymphoma and chronic graft-versus-host disease.1 An association with pulmonary aspergillosis was observed shortly after Ibrutinib was licensed for use.2 A recent phase Ib study of Ibrutinib treatment of primary central nervous system lymphoma reported a 39% incidence of invasive aspergillosis, in patients concurrently treated with corticosteroids, in the absence of neutropenia.3 Studies of Aspergillus fumigatus infection in Btk−/− mice revealed focal pneumonia and large airway mucous plugs, mirroring findings in macrophage-depleted models of pulmonary aspergillosis.

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