Call for Action: Invasive Fungal Infections Associated With Ibrutinib and Other Small Molecule Kinase Inhibitors Targeting Immune Signaling Pathways
Open accessAbstract
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.
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Treatment of patients with lymphoproliferative malignancies with inhibitors of BTK has resulted in a surge in cases of invasive aspergillosis.
“Notably, treatment of patients with lymphoproliferative malignancies with inhibitors of BTK has resulted in a surge in cases of invasive aspergillosis (79, 264).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [79]
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- Authors
- Chamilos, G., Lionakis, M. S., & Kontoyiannis, D. P.
- Affiliations
- University of Crete (GR)
- National Institutes of Health (US)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Kontoyiannis, Dimitrios P
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-09-27
- Volume
- 66
- Issue
- 1
- Pages
- 140-148
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC5850040
- OpenAlex
- W2759554330
- Cited by
- 267
- References
- 67
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 22 · 2023: 28 · 2022: 22 · 2021: 44 · 2020: 45 · 2019: 37 · 2018: 39 · 2017: 3
- FWCI
- 26.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Infectious Diseases (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
- Health Sciences › Medicine › Epidemiology › Pneumocystis jirovecii pneumonia detection and treatment
- Keywords
- invasive fungal infections, ibrutinib, BTK inhibitors, small-molecule kinase inhibitors, opportunistic infections, Pneumocystis jirovecii, Cryptococcus neoformans, hematologic malignancies, immunosuppression, immune signaling pathways, risk stratification, hematopoietic stem cell transplantation
- MeSH terms
- Invasive Fungal Infections, Adenine, Aged, Aged, 80 and over, Female, Fungi, Humans, Immunosuppressive Agents, Male, Middle Aged, Piperidines, Pyrazoles, Pyrimidines, Signal Transduction, Hematologic Neoplasms, Protein Kinase Inhibitors
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