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Ibrutinib BTK Fungal Risk — SCE Infectious Diseases MCQ

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HardImmunocompromised HostIbrutinib BTK Fungal RiskSCE Infectious Diseases

A 60-year-old man on Ibrutinib for CLL develops invasive aspergillosis. Why is Ibrutinib specifically associated with increased fungal infection risk?

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Correct answer: B — Ibrutinib inhibits Bruton tyrosine kinase (BTK) which is expressed in macrophages and neutrophils — impairing innate immune antifungal responses, particularly against Aspergillus

Ibrutinib inhibits BTK, which is expressed not only in B-cells but also in macrophages and neutrophils. BTK is involved in innate antifungal immunity. This explains the increased rate of invasive aspergillosis seen in the first 6 months of Ibrutinib therapy, independent of neutropenia. Treatment interaction: Voriconazole/Posaconazole strongly inhibit CYP3A4, dramatically increasing Ibrutinib levels — Isavuconazole or dose-adjusted Voriconazole with TDM is preferred.

Reference: Lancet Haem 2021 – Ibrutinib and IFD; BSAC 2024 – Antifungal guidelines