The U.S. Food and Drug Administration approved rituximab (Rituxan/MabThera, Roche/Genentech) as a maintenance treatment for patients with advanced follicular lymphoma who responded to initial treatment with rituximab plus chemotherapy (induction treatment). This milestone follows the clearance of rituximab for this indication by the European Commission in October 2010.

Rituximab is a therapeutic antibody that binds to the CD20 antigen on the surface of normal and malignant B-cells. It then recruits the body’s natural defenses to attack and kill the marked B-cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return to normal levels within several months.

The drug first received FDA approval in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent. It was approved in the European Union in June 1998.

?This approval is important because it shows that maintenance treatment with rituximab after initial therapy with rituximab and chemotherapy, further reduces the risk of relapse in people with follicular lymphoma,? said Hal Barron, M.D., Head of Global Development and Chief Medical Officer at Roche. ?Maintenance use of Rituxan/MabThera offers people with this incurable disease the opportunity to live longer without their disease getting worse, a primary goal of treatment.?

Follicular lymphoma (FL), a cancer of the blood, is a common type of non-Hodgkin?s lymphoma (NHL). Follicular lymphoma is considered incurable and is characterised by periods of relapse and remission over a number of years. Require additional treatments can lead to fatal outcomes. This approval, based on the PRIMA study, showed continuing rituximab administration every two months for two years in patients who responded to initial treatment with rituximab plus chemotherapy, nearly doubled the likelihood of them living without their disease worsening (progression-free survival or PFS) compared to those who stopped treatment (based on a hazard ratio of 0.54, 95% CI, 0.42?0.70; p<=0.0001).

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Approximately 286,000 people worldwide are diagnosed with NHL each year1, and follicular lymphoma accounts for about 1 in 5 of these cases. According to the American Cancer Society (ACS), an estimated 574,000 Americans are living with non-Hodgkin?s lymphoma (NHL). Approximately 65,540 Americans will have been newly diagnosed with NHL in the United States in 2010. Of those diagnosed with NHL, 1 in 5 patients will have follicular lymphoma.

Clinical trial
This approval by the U.S. FDA was based on data from a Phase III study, PRIMA. Sponsored by the Groupe d’Etude des Lymphomes de l’Adulte (GELA), PRIMA is an international, multicenter, randomised, phase III clinical study that enrolled 1,217 patients with previously untreated advanced follicular lymphoma. The study evaluated the efficacy and safety profile of maintenance rituximab in patients who achieved a response (complete or partial) to rituximab in combination with chemotherapy.

In the study, eight cycles of rituximab plus either CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), CVP (cyclophosphamide, vincristine and prednisone) or FCM (fludarabine, cyclophosphamide and mitoxantrone) chemotherapy was used as initial treatment. Patients who responded to this initial treatment and were eligible for maintenance treatment (1,018/1,217) were randomised to receive rituximab as a single-agent maintenance therapy, given once every two months for two years (maintenance), or to observation alone.

The safety profile was consistent with those previously reported in pivotal studies of rituximab alone or in combination with chemotherapy. Grade ? 2 infections were reported more frequently in patients who received rituximab maintenance compared to the observation arm (37% vs. 22%). Grade 3-4 adverse reactions occurring at a higher incidence (? 2%) in the rituximab group were infections (4% vs. 1%) and neutropenia (4% vs. <1%).

[1] Lymphoma Coalition Last accessed November 2010.

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