The safety of Bruton's tyrosine kinase inhibitors in B-cell malignancies: A systematic review

Michael Arustamyan, Pavel Kibrik, Dilara Hatipoglu, Brandon Bungo, Amgad Mentias, Brian T. Hill, Rohit Moudgil*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

B-cell malignancies, most notably lymphomas, make up most of the non-Hodgkin lymphomas in the United States. There are limited randomized data comparing first- and second-generation Bruton tyrosine kinase (BTK) inhibitors. Our aim was to compare the safety profiles of first versus second-generation BTK inhibitors. A systematic search was performed from database inception to January 13, 2020. Studies with BTK inhibitor monotherapy for the treatment of B-cell malignancies in the adult population (>18 years old) were utilized and the adverse events (AEs) were extracted. Fifty-five studies that met the inclusion criteria were included in the systematic review with 41 studies with first generation and 14 studies with second generation. The review included both clinical trials and retrospective studies with average time of follow-up of 2 years for the first-generation group and 18 months for the second-generation group. We found that the incidence of cardiovascular AEs was significantly higher in the first-generation group (20.8%) as compared to the second-generation group (6.3%). However, there was a higher incidence of hematologic/oncologic and gastrointestinal side effects in the second-generation group compared to the first (62.3% compared to 39.2% and 36.9% compared to 28.9%). The number of Grade 5 cardiovascular events (death) was same in the first-generation group compared to the second generation. Further research is needed to develop highly selective BTK inhibitors to avoid unwanted AEs by minimizing off-targets.

Original languageEnglish (US)
Pages (from-to)696-710
Number of pages15
JournalEuropean Journal of Haematology
Volume109
Issue number6
DOIs
StatePublished - Dec 2022

Keywords

  • B-cell malignancies
  • bruton tyrosine kinase inhibitors
  • systematic review

ASJC Scopus subject areas

  • Hematology

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