Does Combined Immunochemotherapy with the Monoclonal Antibody Rituximab Improve Overall Survival in the Treatment of Patients with Indolent Non-Hodgkin Lymphoma? Preliminary Results of a Comprehensive Meta-Analysis.

Abstract Background: The monoclonal anti-CD20 antibody Rituximab (R) has been shown to induce high response rates and to improve progression free survival when added to combined chemotherapy in newly diagnosed and relapsed indolent lymphoma. It remains unclear if R combined with chemotherapy may also have an impact on overall survival (OS). Objectives: To determine the effectivness of a combination chemotherapy plus R versus chemotherapy alone with respect to overall survival. Methods: Randomized controlled trials (RCT) comparing chemotherapy plus R vs chemotherapy alone in patients with newly diagnosed or relapsed indolent lymphoma and mantle cell lymphoma. Medical databases (Cochrane Library, MEDLINE, EMBASE) and conference proceedings were searched (1990–2005). We included full-text and abstract publications. Data extraction and quality assessment were done in duplicate. Data were pooled under a fixed-effects model. Number needed to treat were calculated to facilitate interpretation. Main results: We identified six eligible RCTs involving patients with follicular and mantle cell lymphoma. Treatment regimen combined with R were CHOP (2x), CNOP, CVP, FCM and MCP. A total of 5 trials with 994 randomized untreated pts were included in the survival analysis. The included studies were described by the authors as randomized. In all studies, the method for allocation concealment could not be determined. Three studies were published as full text, and two were abstract publications. Overall survival was statistically significantly improved in the R-chemotherapy group compared to chemotherapy alone (HR 0.61; 95%-CI: 0.47–0.80). There was no statistical heterogeneity between the trials compared. Assuming a survival chance of 85% after 18 months for patients with low grade NHL we estimated that it would be necessary to treat 17 (95%-CI: 13–33) patients with R in addition to chemotherapy to prevent one death. For patients with mantle cell lymphoma and a survival chance of 60% after 18 months the corresponding estimate is 6 (95%-CI: 5–13). Conclusion: This preliminary meta-analysis demonstrated evidence for improved overall survival among patients with indolent lymphoma and mantle cell lymphoma treated with a combination of rituximab plus chemotherapy compared to chemotherapy alone.