Roche files MabThera for new maintenance lymphoma indication in EU
This article was originally published in Scrip
Roche has filed its blockbuster non-Hodgkin's lymphoma (NHL) drug MabThera (rituximab) for an additional indication for the disease in the EU, maintenance treatment for previously untreated patients with advanced follicular lymphoma.
Rituximab, an anti-CD20 monoclonal antibody that targets B-cells, discovered by Biogen Idec, is considered standard of care in the first-line setting in NHL in combination with chemotherapy.
In the EU, MabThera does have a maintenance indication as well, but for patients with relapsed or refractory follicular lymphoma. About 20-30% of NHL patients have follicular lymphoma (FL), a slow-growing (low-grade), but incurable form of NHL. Although FL progresses slowly, the median survival time is seven to 10 years.
The new filing is based on the Phase III PRIMA study which was designed to explore the efficacy of MabThera maintenance therapy following induction treatment with MabThera and chemotherapy in previously untreated patients with advanced follicular lymphoma. It met its primary endpoint of progression-free survival (PFS) during a pre-planned interim analysis in September 2009 (scripnews.com 21 September 2009). Data from the trial will be presented at the upcoming ASCO meeting in June in Chicago.
The PRIMA study, which was sponsored by the Groupe d'Etudes de Lymphomes de L'Adulte (GELA), and supported by the companies, evaluated maintenance Rituxan in patients who responded to initial treatment with rituximab plus chemotherapy (they had to have either a complete or partial response).
In the study, rituximab plus chemotherapy was used as initial treatment for six months. Patients who responded were randomised to receive rituximab alone, given once every two months for two years, or observation alone.
The study was not designed to address the important question of whether maintenance therapy with rituximab prolongs overall survival compared with giving it in the first-line setting, followed by a treatment holiday for patients until their disease relapses, and then re-treating them in the second-line with rituximab again.
Roche told Scrip that it planned to file the PRIMA data with the US FDA later this month. In the US, since 2006, rituximab (known as Rituxan in the US) has also had an indication in the maintenance setting, specifically for use following non-progressing (including stable disease), low-grade NHL as a single agent following first-line CVP therapy. This is based on a 311-patient Phase III trial, ECOG 1496, which found that rituximab prolonged PFS in this setting.
However, the ECOG 1496 trial did not address the question of whether maintenance rituximab would be still be effective following first-line treatment with rituximab plus chemotherapy, a key question given that this combination is now standard-of-care in previously untreated FL.
Bayer's Zevalin ([90Y]-ibritumomab tiuxetan) has a first-line maintenance indication in the US and EU. The radioimmunotherapy extended median PFS from 13.5 months to 37 months in the 414-patient FIT trial. However, most patients had induction chemotherapy only, while just 59 had chemotherapy with rituximab. The trial's lead investigator previously told Scrip that it was not known whether Zevalin would have added the benefit observed in this trial if all patients had received induction treatment with chemotherapy and rituximab.
Zevalin targets malignant B-cells with a monoclonal antibody against the CD20 antigen like rituximab and additionally kills them with beta-radiation emitted by yttrium-90. The method concentrates radiation at the site of tumours, thus minimising its systemic effects.