Fungal Infections with Ibrutinib and Other Small-Molecule Kinase Inhibitors

TY - JOUR

T1 - Fungal Infections with Ibrutinib and Other Small-Molecule Kinase Inhibitors

AU - Zarakas, Marissa A.

AU - Desai, Jigar V.

AU - Chamilos, Georgios

AU - Lionakis, Michail S.

N1 - Publisher Copyright: © 2019, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

PY - 2019/9/15

Y1 - 2019/9/15

N2 - Purpose of Review: Small-molecule kinase inhibitors (SMKIs) have revolutionized the management of malignant and autoimmune disorders. Emerging clinical reports point towards an increased risk for invasive fungal infections (IFIs) in patients treated with certain SMKIs. In this mini-review, we highlight representative examples of SMKIs that have been associated with or are expected to give rise to IFIs. Recent Findings: The clinical use of the Bruton’s tyrosine kinase inhibitor ibrutinib as well as other FDA-approved SMKIs has been associated with IFIs. The fungal infection susceptibility associated with the clinical use of certain SMKIs underscores their detrimental effects on innate and adaptive antifungal immune responses. Summary: The unprecedented development and clinical use of SMKIs is expected to give rise to an expansion of iatrogenic immunosuppressive factors predisposing to IFIs (and other opportunistic infections). Beyond increased clinical surveillance, better understanding of the pathogenesis of SMKI-associated immune dysregulation should help in devising improved risk stratification and prophylaxis strategies in vulnerable patients.

AB - Purpose of Review: Small-molecule kinase inhibitors (SMKIs) have revolutionized the management of malignant and autoimmune disorders. Emerging clinical reports point towards an increased risk for invasive fungal infections (IFIs) in patients treated with certain SMKIs. In this mini-review, we highlight representative examples of SMKIs that have been associated with or are expected to give rise to IFIs. Recent Findings: The clinical use of the Bruton’s tyrosine kinase inhibitor ibrutinib as well as other FDA-approved SMKIs has been associated with IFIs. The fungal infection susceptibility associated with the clinical use of certain SMKIs underscores their detrimental effects on innate and adaptive antifungal immune responses. Summary: The unprecedented development and clinical use of SMKIs is expected to give rise to an expansion of iatrogenic immunosuppressive factors predisposing to IFIs (and other opportunistic infections). Beyond increased clinical surveillance, better understanding of the pathogenesis of SMKI-associated immune dysregulation should help in devising improved risk stratification and prophylaxis strategies in vulnerable patients.

KW - Aspergillosis

KW - Cryptococcosis

KW - Ibrutinib

KW - Invasive fungal infections

KW - Pneumocystis jirovecii pneumonia

KW - Small-molecule kinase inhibitors

UR - https://www.scopus.com/pages/publications/85068830030

U2 - 10.1007/s12281-019-00343-9

DO - 10.1007/s12281-019-00343-9

M3 - Review article

SN - 1936-3761

VL - 13

SP - 86

EP - 98

JO - Current Fungal Infection Reports

JF - Current Fungal Infection Reports

IS - 3

ER -