Heterogeneity in Infection Reporting Across Covalent Bruton Tyrosine Kinase Inhibitor Studies in B-Cell Malignancies: A Systematic Review

Abstract

Bruton tyrosine kinase inhibitors (BTKis) have transformed the management of B-cell malignancies but are associated with clinically important infectious complications. Interpretation and comparison of infectious risk across studies remain challenging because reporting practices vary considerably. We systematically reviewed 40 clinical trials and cohort studies including 5,486 BTKi-treated patients published between 2013 and 2025 to characterize infectious outcome reporting. Upper respiratory tract infections, pneumonia, and urinary tract infections were the most frequently reported, while opportunistic fungal and viral infections were reported inconsistently. Only 11 studies described antimicrobial prophylaxis, and substantial variability was observed in infection severity grading, follow-up duration, adverse-event reporting, and attribution of infection-related mortality. These inconsistencies limit meaningful comparisons of infectious risk across BTKi studies and may confound interpretation of apparent differences between agents. Standardized reporting of infectious outcomes and prophylactic strategies is needed to improve future clinical trials and facilitate evidence-based infection prevention in patients receiving BTKi therapy.