OBJECTIVES: Bruton's tyrosine kinase inhibitors (BTKi) have demonstrated promising efficacy outcomes in numerous B-cell lymphoma subtypes. However, patients treated with BTKi are at an increased risk of severe infections. This systematic review and meta-analysis aims to determine the risk of severe infections associated with BTKi monotherapy in patients with B-cell lymphoma.

METHODS: MEDLINE/PubMed, Embase, and Web of Science databases were searched from their inception until October 4, 2023. Additional records were identified through searches of ClinicalTrials.gov, bibliographies, and relevant conference abstracts. Randomized controlled trials (RCTs) reporting on patients treated with BTKi monotherapy for any type of B-cell lymphoma and infections were included. The meta-analysis was conducted using a random-effects model and the risk ratio (RR) was calculated using the Mantel-Haenszel method in R Statistical Software, version 4.3.2.

RESULTS: A total of 3,289 studies were retrieved from the databases. Eleven studies were included in the review, and six of these studies were included in the meta-analysis. The median age of patients across the studies ranged from 64 to 73 years, and the median follow-up ranged from 9.4 to 44.4 months. Overall, the meta-analysis included 1,772 patients in the intervention group and 1,676 in the comparator group. In patients treated with BTKi, the incidence of Grade ≥ III infections (including pneumonia, upper respiratory tract, and urinary tract infection) was higher compared to the comparator group. The RR was 1.64 with a 95% confidence interval of 1.03-2.61, p-value: 0.036.

CONCLUSIONS: Patients with B-cell lymphoma who are treated with BTKi monotherapy are at an increased risk of developing severe infections. Clinicians should be aware of the potential infectious events that can occur when prescribing BTKi monotherapy. It is essential to closely monitor for infections and to develop effective prophylactic strategies for patients with B-cell lymphoma treated with BTKi monotherapy.