Rituximab as maintenance therapy for patients with follicular lymphoma

Follicular lymphoma is a B-cell lymphoma characterised by an initial response to treatment that is usually followed by relapse and progression. Most patients present with advanced disease that cannot be cured. Lymphoma B-cells express CD20. Rituximab, a monoclonal anti-CD20 antibody, is expected to be active against cells that express CD20. Compared to chemotherapy alone, rituximab in combination with chemotherapy improves overall survival when used for induction therapy (treatment designed as a first step toward reducing the number of cancer cells) for patients with newly diagnosed or relapsed indolent lymphoma. Clinical trials that have shown improved event-free survival were inconsistent regarding overall (all-cause) survival. We aimed to evaluate the effects of maintenance therapy with rituximab on overall survival in patients with follicular lymphoma.

Study design: systematic review and meta-analysis of five randomised controlled trials (1056 patients).
Contribution: patients with follicular lymphoma and high tumour burden treated with rituximab maintenance therapy had better overall survival and disease control but more infections than patients who were observed without rituximab.
Implications: rituximab maintenance therapy should be added to the standard therapy of patients with relapsed or refractory (to treatment) follicular lymphoma following a successful induction treatment.
Limitations: variability in treatment regimens among trials precluded determination of the optimal rituximab maintenance regimen. One trial compared rituximab maintenance to rituximab at disease progression for patients with lower tumour burden and found both options to be comparable.
Future research should focus on:
the effect of rituximab maintenance compared to rituximab at progression;
defining which patients benefit the most from rituximab, according to burden of disease, prognostic score, the type of chemotherapy regimens used for induction, and the inclusion of rituximab in induction; and
the optimal duration of maintenance treatment, as well as its schedule.
Both randomised controlled trials and observational trials should have longer follow up in order to assess the long-term toxicity of rituximab, and should evaluate quality of life outcomes.

Authors' conclusions: 

Rituximab maintenance therapy should be added to standard therapy of patients with relapsed or refractory follicular lymphoma following a successful induction treatment. The drug should be given either as four weekly infusions every six months or as a single infusion every two to three months. Future randomised controlled trials should explore the effect of different protocols of rituximab maintenance therapy on overall survival.

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Background: 

Rituximab, a monoclonal anti-CD20 antibody, in combination with chemotherapy improves overall survival compared to chemotherapy alone when used for induction therapy for patients with newly diagnosed or relapsed indolent lymphoma. Randomised controlled trials have demonstrated that maintenance treatment with rituximab prolongs progression-free survival but evidence of effect on overall survival is lacking.

Objectives: 

To evaluate the effects of maintenance treatment with rituximab on overall survival in patients with follicular lymphoma.

Search strategy: 

We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), PubMed (June 2007), EMBASE (June 2007), LILACS (June 2007), databases of ongoing trials, and relevant conference proceedings. References of identified trials were searched and the first author of each included trial was contacted.

Selection criteria: 

Randomised controlled trials that compared rituximab maintenance therapy to observation, treatment at relapse (no maintenance therapy), or other maintenance treatment.

Data collection and analysis: 

Two authors independently appraised the quality of each trial and extracted data from included trials. Hazard ratios (HR) and relative risks with 95% confidence intervals (CI) were estimated and pooled using the fixed-effect model.

Main results: 

Five trials including 1056 adult patients were included in the review. Four trials (895 patients) were included in the analysis of overall survival. Patients treated with rituximab as maintenance therapy had a significantly better overall survival compared to observation alone (HR 0.53, 95% CI 0.38 to 0.73).

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