Maintenance therapy with rituximab (Rituxan) improved survival in patients with relapsed or refractory follicular lymphoma who responded to induction therapy, according to a systematic review and meta-analysis of randomized, controlled trials presented at the 52nd Annual Meeting of the American Society of Hematology.¹ Maintenance rituximab improved progression-free survival both after first-line treatment and in relapsed or refractory follicular lymphoma, and improved overall survival in relapsed or refractory follicular lymphoma, despite a higher rate of infection. The meta-analysis included eight randomized, controlled trials that compared maintenance rituximab therapy with observation or treatment at relapse.

Benefit Confirmed

"This meta-analysis confirms the benefit of maintenance rituximab in follicular lymphoma, showing prolonged progression-free survival for all patients with follicular lymphoma," stated Anat Gafter-Gvili, MD, Tel Aviv University in Tel Aviv, Israel, who was second author of this poster presentation.

Although follicular lymphoma is considered an indolent lymphoma, patients typically relapse after therapy and experience disease progression. Most patients present with advanced disease and are not curable with current therapy. The poster presentation at the ASH meeting updated a previous meta-analysis and included four more recent clinical trials.²

Updated Findings

The trials were identified by a search of several databases, including The Cochrane Library, MEDLINE, EMBASE, LILACS, and proceedings of important conferences between 2000 and 2010, including ASH, ASCO, and EHA. All trials had overall survival as the primary outcome. Eight trials fulfilled criteria for the meta-analysis; median follow-up ranged from 25 months to 9.5 years.

Maintenance rituximab significantly improved overall survival compared with observation or treatment at relapse (no maintenance therapy) in a total of 2,283 patients. The hazard ratio for death was 0.75 (95% CI = 0.61-0.91).

Maintenance rituximab also significantly improved progression-free survival compared with observation or treatment at relapse, regardless of whether it was initiated after first-line or subsequent therapy, and regardless of the type of induction therapy administered.  Induction therapy included rituximab alone (n = 240 patients), chemotherapy alone (n = 208 patients), and rituximab plus chemotherapy (n = 1,352 patients).

More infection-related adverse events occurred with maintenance rituximab than with observation alone or treatment at relapse (risk ratio = 1.99; 95% CI = 1.21-3.27). Overall, rituximab maintenance was associated with a higher rate of grade 3/4 adverse events (risk ratio = 1.47; 95% CI = 1.19-1.83).

Three of the eight trials were stopped early after benefit of maintenance was shown. Dr. Gafter-Gvili and colleagues suggested that stopping trials early can overestimate treatment effects. ■

Editor's note: In January 2011, the FDA approved rituximab (Rituxan) as a maintenance therapy for advanced follicular lymphoma in patients who responded to induction therapy with rituximab plus chemotherapy. Approval of rituximab as maintenance therapy was based on results of the PRIMA study (Primary Rituxan and Maintenance), sponsored by the Groupe d'Etude des Lymphomes de l'Adulte (GELA). The PRIMA study was published in Lancet 377(9759):42-51, 2011.

References

1. Vidal L, Gafter-Gvili A, Salles G, et al: Rituximab maintenance for the treatment of patients with follicular lymphoma: Systematic review and meta-analysis of randomized trials-2010 update. 52nd ASH Annual Meeting. Abstract 1798. Presented December 4, 2010.

2. Vidal L, Gafter-Gvili A, Leibovici L, et al: Rituximab maintenance for treatment of patients with follicular lymphoma: Systematic review and meta-analysis of randomized trials. J Natl Cancer Inst 101:248-255, 2009.