Four RCTs with 1,688 randomised participants were included in the review. Trials compared cyclophosphamide, vincristine and prednisolone (CVP), cyclophosphamide, doxorubicin/adriamycin, vincristine and prednisolone (CHOP), mitoxantrone, chlorambucil and prednisolone (MCP) and cyclophosphamide, doxorubicin, etoposide, prednisolone and interferon-alpha (CHVPi) chemotherapies (details in the report) with the same regimen plus rituximab. Median follow-up ranged from 47 to 60 months. All four trials were rated adequate for randomisation, allocation concealment, power calculation and intention-to-treat analysis but none reported blinded outcome assessment. Follow-up was at least 80% in all trials.
Overall survival ranged from 83% to 90% in the rituximab-chemotherapy groups and from 77% to 84% in the chemotherapy-alone groups. The difference between groups was statistically significant in three trials. Results from two trials were confounded by the effects of subsequent therapy provided to all responders to first-line treatment.
Overall response rates were significantly improved by rituximab in all four trials. A significant improvement in complete response rates was reported in two trials. Exploratory meta-analyses (details in the report) showed a significant difference for most response outcomes but heterogeneity was high (Ι²=56 to 88%). There was no additional toxicity of clinical relevance with chemotherapy plus rituximab versus chemotherapy alone.