Immunochemotherapy with Rituximab and Overall Survival in Patients with Indolent or Mantle Cell Lymphoma: a Systematic Review and Meta-analysis

Background: Addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy (R-chemo) has been shown to improve response rates and progression-free survival in patients with indolent or mantle cell lymphoma. However, the impact of R-chemo on overall survival is unclear. We performed a comprehensive systematic review and meta-analysis to examine the efficacy of combined immunochemotherapy using R-chemo compared with the identical chemotherapy alone with respect to overall survival in patients with advanced indolent lymphoma or mantle cell lymphoma.

Methods: Medical databases and conference proceedings were searched for randomized controlled trials published from January 1990 through December 2005 that compared R-chemo with chemotherapy alone in patients with newly diagnosed or relapsed indolent lymphoma or mantle cell lymphoma. We included full-text and abstract publications. Endpoints were overall survival, disease control, overall response, and toxicity. A fixed-effects model was assumed in all meta-analyses. For binary data, the relative risk was used as an indicator of treatment effect, and the Mantel-Haenszel method was used to pool relative risks. Statistical tests for heterogeneity were one-sided; statistical tests for effect estimates were two-sided.

Results: Seven randomized controlled trials involving 1943 patients with follicular lymphoma, mantle cell lymphoma, or other indolent lymphomas were included in the meta-analysis. Five studies were published as full-text articles, and two were in abstract form. Patients treated with R-chemo had better overall survival (hazard ratio [HR] for mortality = 0.65; 95% confidence interval [CI] = 0.54 to 0.78), overall response (relative risk of tumor response = 1.21; 95% CI = 1.16 to 1.27), and disease control (HR of disease event = 0.62; 95% CI = 0.55 to 0.71) than patients treated with chemotherapy alone. R-chemo improved overall survival in patients with follicular lymphoma (HR for mortality = 0.63; 95% CI = 0.51 to 0.79) and in patients with mantle cell lymphoma (HR for mortality = 0.60; 95% CI = 0.37 to 0.98). However, in the latter case, there was heterogeneity among the trials (P = .07), making the survival benefit less reliable.

Conclusion: In patients with indolent or mantle cell lymphoma, R-chemo is superior to chemotherapy alone with respect to overall survival.