Rituximab maintenance therapy for follicular lymphoma: no better than watchful waiting.

Chemotherapy is the first-choice treatment for patients with advanced follicular lymphoma (Ann Arbor stage III or IV) who qualify for therapy, but there is no consensus protocol. Adding rituximab (Mabthera, Roche) to chemotherapy moderately improves survival time. Rituximab is now authorised for long-term maintenance therapy in patients with follicular lymphoma in whom first-line chemotherapy induces a response. Clinical evaluation of rituximab in this setting is based on two unblinded randomised trials comparing rituximab maintenance therapy with watchful waiting in 1193 and 401 patients. Neither trial showed that rituximab had an impact on mortality or quality of life. Rituximab prolonged progression-free survival, based on unblinded assessment of radiological, laboratory or clinical criteria. These trials suffer from biases that make it difficult to interpret the results, including the lack of blinding, premature termination and too short follow-up in the larger trial, and in the other trial, heterogeneous patient recruitment and use of a different dose regimen from that recommended in the summary of product characteristics. Both trials confirmed the adverse effect profile of rituximab, which includes haematological disorders, infections, and cardiac and digestive disorders. These adverse effects are severe in about 7% of patients. There is also a riskof musculoskeletal and neuropsychiatric disorders. Questions still persist abouta possible oncogenic effect. In practice, the benefits of long-term rituximab maintenance therapy after a first line of chemotherapy remain to be demonstrated in terms of the length or quality of survival in patients with follicular lymphoma, while adverse effects are noteworthy. Pending further data, rituximab should only be used in clinical trials in this specific setting.