TY - JOUR
T1 - Call for Action
T2 - Invasive Fungal Infections Associated with Ibrutinib and Other Small Molecule Kinase Inhibitors Targeting Immune Signaling Pathways
AU - Chamilos, Georgios
AU - Lionakis, Michail S.
AU - Kontoyiannis, Dimitrios P.
N1 - Funding Information:
Financial support. This work was supported in part by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (M. S. L.), the Greek State Scholarship Foundation (IKY) (G. C.), and the Texas 4000 Distinguished Professorship Endowment for Cancer Research (D. P. K.). Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Opportunistic infections caused by Pneumocystis jirovecii, Cryptococcus neoformans, and ubiquitous airborne filamentous fungi have been recently reported in patients with hematological cancers historically considered at low risk for invasive fungal infections (IFIs), after receipt of the Bruton tyrosine kinase inhibitor ibrutinib. The spectrum and severity of IFIs often observed in these patients implies the presence of a complex immunodeficiency that may not be solely attributed to mere inhibition of Bruton tyrosine kinase. In view of the surge in development of small molecule kinase inhibitors for treatment of malignant and autoimmune diseases, it is possible that there would be an emergence of IFIs associated with the effects of these molecules on the immune system. Preclinical assessment of the immunosuppressive effects of kinase inhibitors and human studies aimed at improving patient risk stratification for development of IFIs could lead to prevention, earlier diagnosis, and better outcomes in affected patients.
AB - Opportunistic infections caused by Pneumocystis jirovecii, Cryptococcus neoformans, and ubiquitous airborne filamentous fungi have been recently reported in patients with hematological cancers historically considered at low risk for invasive fungal infections (IFIs), after receipt of the Bruton tyrosine kinase inhibitor ibrutinib. The spectrum and severity of IFIs often observed in these patients implies the presence of a complex immunodeficiency that may not be solely attributed to mere inhibition of Bruton tyrosine kinase. In view of the surge in development of small molecule kinase inhibitors for treatment of malignant and autoimmune diseases, it is possible that there would be an emergence of IFIs associated with the effects of these molecules on the immune system. Preclinical assessment of the immunosuppressive effects of kinase inhibitors and human studies aimed at improving patient risk stratification for development of IFIs could lead to prevention, earlier diagnosis, and better outcomes in affected patients.
KW - Ibrutinib
KW - invasive fungal infections
KW - opportunistic infections
KW - small molecule tyrosine kinase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85040547179&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040547179&partnerID=8YFLogxK
U2 - 10.1093/cid/cix687
DO - 10.1093/cid/cix687
M3 - Article
C2 - 29029010
AN - SCOPUS:85040547179
SN - 1058-4838
VL - 66
SP - 140
EP - 148
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 1
ER -