Call for Action: Invasive Fungal Infections Associated With Ibrutinib and Other Small Molecule Kinase Inhibitors Targeting Immune Signaling Pathways.

Abstract

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.

• Authors: Georgios Chamilos, Michail S Lionakis, Dimitrios P Kontoyiannis
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 66 Issue 1 Pg. 140-148 (01 06 2018) ISSN: 1537-6591 [Electronic] United States
• PMID: 29029010 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Immunosuppressive Agents
• Piperidines
• Protein Kinase Inhibitors
• Pyrazoles
• Pyrimidines
• ibrutinib
• Adenine

Topics

• Adenine (analogs & derivatives)
• Aged
• Aged, 80 and over
• Female
• Fungi (classification, isolation & purification)
• Hematologic Neoplasms (complications, drug therapy)
• Humans
• Immunosuppressive Agents (administration & dosage, adverse effects)
• Invasive Fungal Infections (epidemiology)
• Male
• Middle Aged
• Piperidines
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Pyrazoles (administration & dosage, adverse effects)
• Pyrimidines (administration & dosage, adverse effects)
• Signal Transduction (drug effects)