Rituximab maintenance for the treatment of patients with follicular lymphoma: Systematic review and meta-analysis of randomized trials

Background: Follicular lymphoma is characterized by slow growth and an initially high rate of response to treatment, but patients typically relapse and experience progressive disease. Rituximab in combination with chemotherapy has been shown to improve overall survival in patients with follicular lymphoma compared with chemotherapy alone, but data from randomized clinical trials evaluating rituximab maintenance treatment in these patients are limited. We aimed to evaluate the effect of maintenance treatment with rituximab on the overall survival of patients with follicular lymphoma. Methods: We performed a systematic review and meta-analysis of randomized controlled trials that compared rituximab maintenance therapy with observation or treatment at relapse (no maintenance therapy). We searched The Cochrane Library, PubMed, EMBASE, LILACS, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled. Results: Five trials including 1143 adult patients were included in this meta-analysis. Data for 985 patients with follicular lymphoma were available for the meta-analysis of overall survival. Patients treated with maintenance rituximab had statistically significantly better overall survival than patients in the observation arm or patients treated at relapse (hazard ratio [HR] for death = 0.60, 95% confidence interval [CI] = 0.45 to 0.79). The rate of infection-related adverse events was higher with rituximab maintenance treatment (HR = 1.99, 95% CI = 1.21 to 3.27). Patients with refractory or relapsed (ie, previously treated) follicular lymphoma had a survival benefit with maintenance rituximab therapy (HR for death = 0.58, 95% CI = 0.42 to 0.79), whereas previously untreated patients did not (HR for death = 0.68, 95% CI = 0.37 to 1.25). Conclusions: These results suggest that maintenance therapy with rituximab, either as four weekly infusions every 6 months or as a single infusion every 2-3 months, should be added to standard therapy for patients with relapsed or refractory (ie, previously treated) follicular lymphoma after successful induction therapy. The higher rate of infections with rituximab therapy should be taken into consideration when making treatment decisions.