Rituximab for the first-line treatment of stage III-IV follicular lymphoma

Non-Hodgkin's lymphoma is a cancer of the lymphatic tissue, which causes enlargement of the lymph nodes and generalised symptoms. The lymphatic system produces, stores and delivers lymphocytes, which are cells that fight infection. Follicular lymphoma is a type of low-grade or indolent non-Hodgkin's lymphoma that develops slowly, and often without symptoms, for many years. It affects B-cell lymphocytes and is therefore classified as a B-cell non-Hodgkin's lymphoma. Patients with follicular lymphoma typically present with painless, swollen lymph nodes in the neck, armpit or groin. Systemic or 'B' symptoms are rare and include fever, fatigue, night sweats, and unexplained weight loss.

When a diagnosis of follicular lymphoma is confirmed, investigations are undertaken to find out which areas of the body are affected, the number of lymph nodes involved, and whether other organs are affected, such as the bone marrow or liver. It can be classified into 4 stages of disease (I to IV) that reflect both the number of sites involved and the presence of disease above or below the diaphragm. At most, 10% to 15% of follicular lymphomas are detected at an early stage; the majority of people present with advanced disease (stage III to IV). In 2008, the incidence of follicular lymphoma in England and Wales was 3.4 per 100,000 persons, equating to 1,900 people. More than 70% of follicular lymphomas are diagnosed in people aged over 60 years.

Follicular lymphoma is characterised by a relapsing and remitting clinical course over several years, with each successive response to treatment becoming more difficult to achieve and of shorter duration. In the early 1990s, median survival was expected to be 8 to 10 years. However, in the past decade, longer median survival has been reported (for example, survival at 20 years has been reported to be as high as 44%). Advanced stage III to IV lymphomas eventually become resistant to chemotherapy and transform to high-grade or aggressive lymphomas, such as diffuse large B-cell lymphoma.

Advanced follicular lymphoma is not curable and so the aim of disease management is to both increase life expectancy and to increase health-related quality of life. A proportion of people with stage III to IV follicular lymphoma do not present with symptoms of disease and receive 'watchful waiting' until symptoms occur. Of the people who need systemic therapy, for the majority (90%) first-line therapy is rituximab and chemotherapy, with around two-thirds receiving the CVP regimen as the chemotherapy component of treatment. The next most frequent chemotherapy regimen used with rituximab is CHOP, which accounts for approximately 16% of chemotherapy regimens. People who have a lower performance status may receive chlorambucil as single-agent chemotherapy.

Maintenance treatment is given after response to first-line induction treatment. NICE's technology appraisal guidance on rituximab for the first-line maintenance treatment of follicular non-Hodgkin's lymphoma recommends rituximab monotherapy as an option for maintenance treatment after first-line induction therapy with rituximab plus chemotherapy. After first-line induction therapy (with or without subsequent maintenance therapy), a person's disease eventually relapses, requiring further treatment. The treatment chosen for relapsed disease will depend on the first-line treatment regimen used, the duration of response to treatment and whether the disease has transformed to aggressive lymphoma.