Patients with follicular lymphoma, a slow-growing common type of non-Hodgkin's lymphoma, who are given 2 years of rituximab-maintenance therapy after immunochemotherapy, have significantly better progression-free survival (PFS) and higher response rates compared with patients who do not receive this intervention. These findings from the largest randomised trial of follicular lymphoma to date, published in The Lancet, support rituximab-maintenance therapy as a first-line treatment option for these patients.

Most patients with follicular lymphoma, a cancer of the lymphatic system, respond well to initial treatment, but relapse is common. Over the past decade, the monoclonal antibody rituximab has shown considerable benefit in patients with the disease. Rituximab plus chemotherapy induction regimens have improved overall survival and have become the standard first-line treatment for follicular lymphoma. But the potential benefit of continuing rituximab treatment after completion of chemotherapy is not known.

The PRIMA study was designed to assess the effect of 2 years of rituximab-maintenance therapy on the outcome of patients with follicular lymphoma. 1217 patients with previously untreated follicular lymphoma were enrolled from 223 centres across 25 countries and given an induction regimen of rituximab plus chemotherapy. After induction, 1019 eligible patients who achieved a complete or partial response were then randomly assigned to 2 years of rituximab maintenance (505 patients) or no treatment (513).

Complete response and PFS were determined by clinical examination and CT scans. Patients also completed quality-of-life questionnaires to assess cancer therapy.

After 2 years, 71.5% of patients in the rituximab group achieved complete or unconfirmed complete response compared with 52.2% in the observation group*.

After 3 years, maintenance with rituximab was associated with significantly better PFS (74.9% vs 57.6%) across all subgroups of patients with different demographics, disease characteristics, and prognostic factors. Time to next antilymphoma treatment and next chemotherapy was also longer in the maintenance group.

Interestingly, two quality of life measurements recorded no differences between the groups, suggesting no detrimental effect on quality of life from rituximab maintenance, despite repeated infusions over two years.

Rituximab maintenance therapy was generally well tolerated. However, grade 3 or 4 adverse events were significantly more common in rituximab-maintenance patients (24% vs 17%). The most common side-effects were mild to moderate infections which occurred in 39% of patients taking rituximab compared with 24% in the no treatment group.

The authors conclude: "The data from this study suggest that rituximab maintenance in patients with high tumour burden follicular lymphoma, who respond to rituximab plus chemotherapy induction, improves PFS and should now be considered as first-line treatment for these patients."

In a Comment, Jonathan Friedberg from the University of Rochester, Rochester, USA, says that longer term follow-up of the PRIMA trial is needed to answer questions about long-term safety and resistance before rituximab-maintenance therapy is routinely offered to all patients with follicular lymphoma.

Moreover, he adds: "In an era of increased health-care costs, what benefit is necessary to justify the cost of this maintenance strategy, which at my institution would cost Medicare more than US$60 000 per patient?"


Source: Lancet