Systematic review of infectious events with the Bruton tyrosine kinase inhibitor ibrutinib in the treatment of hematologic malignancies

Objective Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK) in B lymphocytes as well as other kinases including interleukin‐2‐inducible T‐cell kinase (ITK) in CD4+ Th2 regulatory T cells. Increased infections have been observed in patients taking ibrutinib. The overall incidence has not been systematically evaluated. Methods The published literature and conference s of prospective clinical trials using ibrutinib in hematologic malignancies were identified and reviewed using PubMed, Google Scholar, and HemOnc.org per PRISMA guidelines. Infectious events with a focus on pneumonia were collated per the Common Terminology Criteria for Adverse Events Version 4.03 grading. Results Infectious complications are common, occurring in 56% of patients taking single‐agent ibrutinib and 52% of those on combination therapy. Approximately one in 5 patients developed pneumonia, which was the major contributor to a 2% rate of death from infections. Many of the cases of pneumonia were due to opportunistic pathogens. Conclusions Ibrutinib use requires prudent consideration of the impacts on host immunity. We identified a high rate of serious adverse infectious events within prospective clinical trials. Data suggest a role of both BTK and ITK inhibition for the increased events. There was considerable variability in the reporting of adverse events between trials, journals, and conference reports.