A System Review Of Rituximab As Maintenance Therapy For Aggressive B Cell Non-Hodgkin Lymphoma

Objective To assess the efficacy and safety of rituximab maintenance treatment in patients with aggressive B cell non-Hodgkin lymphoma.Methods Randomized controlled trials(RCTs) were searched from Medline/Pub Med, EMBASE, CENTRAL, CBM and Clinical Trials Registry Platform(all up to October first, 2015), as well as from the reference sections of retrieved articles. We included RCTs comparing rituximab maintenance with placebo, no rituximab maintenance or other active maintenance agents for patients with aggressive B cell non-Hodgkin lymphoma. The methodological quality of included RCTs was evaluated and data were extracted, using a specially designed form. The Cochrane Collaboration's Review Manager 5.2 software was used for data analysis. Primary outcome was overall survival(OS), reported as hazard ratio(HR) with 95 % confidence interval(CI). The secondary outcomes included event-free survival(EFS) and progression-free survival(PFS).Results Four trials were identified from 465 references retrieved and 1546 cases were included in this meta-analysis. All these trials compared rituximab maintenance with observation. The maintenance treatment lasted 4 to 24 weeks and the patients were followed up for 3 to 5 years. Three trials reported OS and pooled HR was 0.89 and 95% CI 0.66 to 1.2. Three clinical trials reported EFS and one trial reported FFS As the definition of EFS was the same as FFS; we pooled these four RCTs, HR for EFS was 0.83 and 95% CI 0.72 to 0.96. Two trials reported PFS. Pooled HR for PFS was 0.69 and 95 % CI 0.61 to 0.79. AEs were reported in all four trials. Grade 3 or 4 adverse events were reported in three trials, pooled RR was 1.27 and 95% CI 1.09 to 1.49 and NNH was 4.04. Grade 3 or 4 neutropenia was higher in rituximab than no rituximab group with RR of 2.35(1.38,4.01)and NNH 17.83. Pooled RR for grade 3 or 4 infection was 1.89(1.39,2.58)and NNH 13.60. In subgroup analysis, rituximab maintenance significantly improved EFS and PFS in male patients. In female patients, however, the difference was not significant between maintenance and observation.Conclusions Rituximab maintenance may prolong EFS and PFS but not significantly the OS in aggressive B cell NHL, compared with observation. AEs, especially neutropenia and 3/4 infections were increased. EFS and PFS in male patients might be more likely to benefit from rituximab maintenance.