Hypomethylating Agents-associated Infections-Systematic Review and Meta-analysis of Randomized Controlled Trials

The reported data regarding the effects of hypomethylating agents (HMAs) on the risk of infections seem to be poorly documented and heterogeneous. We conducted a systematic review and meta-analysis of all randomized controlled trials comparing HMA-containing regimens with any other regimen administered to patients with myeloid neoplasms.

A comprehensive search was conducted until February 2018. Two reviewers appraised the quality of the trials and the extracted data. The primary outcome was grade 3/4 infections. The secondary outcomes included febrile neutropenia, fever of unknown origin, grade 3/4 neutropenia, infection-related mortality, and all-cause mortality. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated and pooled. A fixed-effect model was used to pool the data unless significant heterogeneity was present, in which case a random-effects model was used.

We identified 9 trials reported from 2002 to 2016 and randomizing 2184 patients. HMAs were associated with an increase in grade 3/4 infections compared with the comparator (RR, 1.30; 95% CI, 1.02-1.66). This was true for the subgroup of patients aged >60 years (RR, 1.19; 95% CI, 1.01-1.39). In addition, HMAs resulted in an increase in the rate of fever of unknown origin and neutropenia (RR, 1.48; 95% CI, 1.15-1.92; RR, 1.48; 95% CI, 1.22-1.78, respectively). Although no difference was found in the incidence of fatal infections (RR, 1.44; 95% CI, 0.72 to 2.89), treatment with HMA reduced the incidence of all-cause mortality (RR, 0.74; 95% CI, 0.66-0.88).

Treatment with HMAs was associated with an increase in the grade 3/4 infection rate.