Rituximab. Chronic lymphoid leukaemia: no decisive advantage.

When treatment is needed for patients with symptomatic chronic lymphoid leukaemia, the standard first-line treatment is oral chlorambucil. Fludarabine has been used more as a second-line option. Rituximab has been authorised for use in both first-line and second-line therapy. We found no randomised trials comparing rituximab versus either chlorambucil or fludarabine. Clinical evaluation of rituximab is mainly based on 2 randomised unblinded trials, comparing cytotoxic chemotherapy, with and without the addition of rituximab, as first-line treatment in 817 patients in one trial and as second-line treatment in 552 patients in the other trial. Most patients were at a relatively early stage of the disease. After a median follow-up of about 2 years, addition of rituximab increased median progression-free survival by about 7 to 10 months. It was also associated with a higher complete response rate (about 10% to 20% higher). Follow-up was too short to reliably estimate the possible impact on overall survival. In the trial of first-line treatment, adverse events were more frequent in the rituximab group (77% versus 62%), especially serious infections (18% versus 15%) and febrile neutropenia (8% versus 6%). In the trial of second-line therapy, there were more fatal adverse events in the rituximab group (13% versus 10%). Rituximab also carries a risk of progressive multifocal leukoencephalopathy. In practice, adding rituximab to other cytotoxic drugs has no proven benefit in previously untreated patients with chronic lymphoid leukaemia. In second-line treatment, the progression-free survival benefit associated with rituximab must be weighed against the increase in adverse effects.