Risk of Infection Associated With Ibrutinib in Patients With B-Cell Malignancies: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Conflicting reports exist on risk of infection with ibrutinib. We conducted a systematic review and metaanalysis of randomized controlled trials to estimate the relative risk. Ibrutinib use was associated with a statistically significant increased risk of infection in patients with B-cell malignancies. Patients receiving ibrutinib should be vigilantly monitored for development of infections. Introduction: B-cell malignancies confer an increased risk of infection due to associated immune defects. Conflicting evidence exists on the risk of infection in patients receiving ibrutinib. We conducted a systematic review and metaanalysis to estimate relative risk of infection with ibrutinib in B-cell malignancies. Methods: A systematic search of Embase, Medline, Web of Science, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, European Union Clinical Trials Register, and ClinicalTrials.gov was performed through January 15, 2019, to identify randomized controlled trials comparing ibrutinib with other agents or placebo in B-cell malignancies. We pooled point estimates using the Der Simonian and Laird random-effects model. Statistical analyses were performed by Stata/SE 15.1. Results: Seven studies randomizing 2167 patients were included in the final analysis. Treatment duration in studies ranged from 9.4 to 38.7 months. Ibrutinib was associated with a significantly increased risk of infection (any grade and grade 3-5) in patients with B-cell malignancies [pooled risk ratio (RR) = 1.34, 95% confidence interval [CI], 1.06-1.69, P = .015; and RR = 1.35, 95% CI, 1.05-1.74, P = .018, respectively]. In patients with chronic lymphocytic leukemia, a significantly increased risk of grade 3-5 infection was noted in the ibrutinib group [pooled RR = 1.24, 95% CI, 1.02-1.50, P = .028]. Incidences of pneumonia and upper respiratory tract infection were not significantly different between groups. Conclusion: Our meta-analysis found that ibrutinib was associated with significantly higher risk of infections in patients with B-cell malignancies. Occurrence of major individual subtypes was not different between groups, possibly as a result of inconsistent reporting across studies. (C) 2019 Elsevier Inc. All rights reserved.