Invasive Aspergillosis with impaired neutrophil responses against Aspergillus fumigatus in patients treated with Acalabrutinib-findings from three cases

Int J Infect Dis. 2024 May:142:107000. doi: 10.1016/j.ijid.2024.107000. Epub 2024 Mar 8.


Objectives: Ibrutinib, a first-generation covalent Bruton's tyrosine kinase inhibitor (BTKi) was found to be a risk factor for the occurrence of invasive fungal complications. Acalabrutinib is a second-generation covalent BTKi used to treat B-cell malignancies. Healthy donor neutrophils incubated ex vivo with acalabrutinib lose ability to control Aspergillus conidia germination. In patients receiving acalabrutinib, the potential effect on neutrophil antifungal activity is unknown. Furthermore, only two cases of invasive aspergillosis have been reported during treatment with acalabrutinib, outside of a few cases in a clinical trial.

Methods: We describe three new cases of invasive aspergillosis occurring within the first months of acalabrutinib therapy in patients with chronic lymphocytic leukemia. We used videomicroscopy and flow cytometry approaches to investigate the basic functional responses against Aspergillus of neutrophils from acalabrutinib-treated patients.

Results: We showed an alteration in the anti-Aspergillus response after 1 month of acalabrutinb therapy: neutrophils lost their capacities of killing Aspergillus fumigatus germinating conidia and decreased their reactive oxygen species production when stimulated by Aspergillus.

Conclusions: It is important to follow-up patients treated with acalabrutinib for the risk of aspergillosis as well as those treated with ibrutinib.

Keywords: BTK inhibitors; BTKi; Bruton tyrosine kinase; Innate immune response; acalabrutinib; ibrutinib; neutrophils.

Publication types

  • Case Reports

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Aspergillosis* / drug therapy
  • Aspergillus fumigatus*
  • Benzamides*
  • Humans
  • Neutrophils
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazines*


  • Agammaglobulinaemia Tyrosine Kinase
  • acalabrutinib
  • Protein Kinase Inhibitors
  • Benzamides
  • Pyrazines