Bendamustine-associated infections-systematic review and meta-analysis of randomized controlled trials

Data in the literature are lacking regarding the infection-related adverse events of bendamustine-containing regimens. Therefore, we aimed to assess this risk. We conducted a systematic review and meta-analysis of all randomized controlled trials including bendamustine-containing regimens and those administered for any lymphoproliferative disorder or plasma cell dyscrasia compared with any other regimens. A comprehensive search was conducted until December 2015. Two reviewers appraised the quality of trials and extracted data. Primary outcomes were any infections, grade 3 to 4 infections; secondary outcomes were grade 3 to 4 neutropenia and grade 3 to 4 lymphopenia. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated and pooled. A fixed-effect model was used to pool data unless there was significant heterogeneity, in which case a random-effects model was used. Nine trials published between 2006 and 2016 and randomizing 2620 patients were included. There was no statistically significant effect for bendamustine on the rate of any infection (RR 1.09 [95% CI, 0.87-1.36]) or on the rate of grade 3 to 4 infections (RR 1.04 [95% CI, 0.64-1.71]). There was no increase in the rate of grade 3 to 4 neutropenia in the bendamustine arm (RR 0.84 [95% CI, 0.63-1.12]). Our systematic review demonstrates no effect of bendamustine on the rate of infections when compared with either alkylating agents or fludarabine. Thus, bendamustine remains a safe therapeutic option.