Rituximab maintenance therapy dramatically improves survival for patients with lymphoma

EORTC 20981 trial demonstrates: Risk of death can be halved

Two years of maintenance therapy with rituximab dramatically improves the chances of survival for patients suffering from one of the most frequent forms of lymphoma, indolent non-Hodgkin’s Lymphoma (NHL). The EORTC 20981 trial reveals that rituximab maintenance treatment prolongs progression free survival by about 2,5 years, irrespective of initial treatment. Moreover, the risk of death is halved for patients who receive rituximab maintenance therapy, compared to those who receive no maintenance treatment. The outcome of the clinical trial was presented at the 47th annual meeting of the American Society of Hematology in Atlanta, USA, late last year. The final report of the trial is about to be published shortly.

Professor Marinus van Oers M.D. from the Academic Medical Center of the University of Amsterdam, lead investigator of the EORTC pivotal study together with her colleague Professor Anton Hagenbeek, said: “Our trial confirms that rituximab maintenance therapy is highly beneficial for all patients, including those who have already received rituximab as part of their initial therapy. We have not seen such an impressive improvement in progression free and overall survival for indolent NHL in the last 30 years. Maintenance therapy with rituximab may well become the new standard of care for these patients.”

“We are conscious that these results open a new era in the management of indolent NHL“, comments William M. Burns, CEO of the Pharmaceuticals Division at Roche. Based on the findings of the EORTC 20981 trial, Roche has filed with the European authorities for a label extension for rituximab (Mabthera®) maintenance therapy for patients suffering from indolent lymphoma. In Western Europe alone, 20,000 people are newly diagnosed with indolent NHL every year, and around 40,000 are being treated for this disease.

”Besides being a scientific breakthrough, this exemplifies nicely the extent to which the pharmaceutical sector also depends on academic clinical research. One of the aims of EORTC is to bring about innovation in the clinical practice by exploring how drugs already on the market may be used more effectively. The patients, the scientific community and the pharmaceutical industry clearly benefit from our findings: If we hadn't initiated the trial on this ‘academic question’ about rituximab in the first place, no label extension would have been filed”, concludes Patrick Therasse, Director of the EORTC Data Center.

“Which is why policymakers and health care providers committed to promote innovation in clinical practice in Europe should keep this interdependence in mind and promote multi-centre academic clinical research –  both by providing appropriate funding and by ensuring that the legal frameworks are conducive to transnational academic clinical trials.” adds Francoise Meunier, Director General of the EORTC.        

About the study

In the EORTC 20981 trial, 465 patients with relapsed and refractory indolent NHL were randomised to receive either 3-weekly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy or rituximab plus CHOP as induction therapy. Responding patients were then again randomised to either rituximab maintenance, or observation (no further treatment).

Rituximab maintenance therapy was applied as a single infusion of 375mg/m2 every three months over a period of two years. The primary endpoints were response rates and progression-free survival for the initial treatment phase and the maintenance phase of the study, respectively. The trial was performed in 130 centres in Canada, Australia, Netherlands, UK, Norway, Slovenia, Slovakia, Belgium, Hungary, South Africa, Sweden, New Zealand, Denmark, Egypt, France, Switzerland, Italy and Poland.

Results of the induction phase
The results of the induction phase of the trial showed that patients who received rituximab and CHOP (R-CHOP) had a significantly higher rate of complete remission than patients who received CHOP chemotherapy alone (29% vs 16%, p value <0.0001). Furthermore, rituximab and CHOP chemotherapy significantly increased progression free survival compared to CHOP chemotherapy alone (median progression-free survival of 33 months vs 20 months, p value 0.0003).

Results of the maintenance phase
Overall survival (% of patients alive at 3 years)

¹ Treatment effect of maintenance therapy – reduction in the risk of death

Median progression-free survival

² Treatment effect of maintenance therapy – reduction in the risk of progression of the disease, relapse or death

About Non-Hodgkin’s Lymphoma
Non-Hodgkin’s lymphoma (NHL) affects 1.5 million people worldwide. Indolent NHL, representing about 45% of NHL patients, is a slow developing but serious cancer of the lymphatic system. It is currently considered incurable. NHL is one of the fastest growing cancers and has grown in incidence by 80% since the early 1970s.

About Rituximab
Rituximab is a therapeutic antibody that binds to a particular protein - 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.

Rituximab is indicated for the treatment of indolent and aggressive Non-Hodgkin’s Lymphoma. It is known as MabThera® in Europe and as Rituxan® in the United States, Japan and Canada.

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About the EORTC

Created in 1962, the European Organisation for Research and Treatment of Cancer (EORTC) is a not-for-profit international cancer research organisation under the Belgian Law.

EORTC has the mission to develop, conduct, coordinate and stimulate laboratory and clinical research in Europe to improve the management of cancer and related problems by increasing survival but also patients’ quality of life. The ultimate goal of the EORTC is to improve the standard of cancer treatment in Europe, through the development of new drugs and other innovative approaches, and to test more effective therapeutic strategies, using drugs which are already commercially available, or surgery or radiotherapy. EORTC has the aim to facilitate the passage of experimental discoveries into state-of-the-art treatment by keeping to a minimum the time lapse between the discovery of new anti-cancer agents and the implementation of their therapeutic benefit for patients with cancer.

EORTC promotes multidisciplinary cancer research in Europe and is linked to other leading biomedical research organisations around the world. EORTC research takes place in over 300 hospitals, universities and cancer centers in 32 countries and the unique network of investigators of EORTC comprises more than 2000 clinicians collaborating on a voluntary basis in over 20 multidisciplinary groups.

For any further information related to the research activities of the EORTC, please consult the website www.eortc.be