Rituximab

NICE guidance 2003

• Used in combination with CHOP for 1^st line treatment of people with CD20 positive DLBCL at clinical stage II, III or IV
• Not recommended when CHOP contraindicated
• Clinical and cost effectiveness in patients with satge I disease has not been established. In these circumstances should only be used as part of a clinical study

• Background
• 80-85% of NHL are derived form B lymphocytes
• DLBCL is usually fatal within months if left untreated, however they are potentially curable with intensive chemotherapy
• Incidence is 15 in 100, 000
• 7^th most common cancer in UK
• 3-10% of AIDS patients develop aggressive NHL, usually large cell
• 8 CHOP – 40-50% achieve CR, 3 year survival of 30%
• 3 CHOP in stage 1 – 90% achieve CR, 5 year disease free survival of 80-85%
• Standard treatment for stage I disease is 3 chop and involved field radiotherapy

• Rituximab
• Chimeric genetically engineered monoclonal antibody that targets CD20
• CD20 expressed on almost all B cell lymphomas and testing for its presence is part of normal diagnostic procedures
• Suitable target because it doesn’t circulate freely in the plasma, isn’t shed from the cell surface or internalised
• Occurs on normal and malignat B cells, but not B cell precursors
• Induces death via
• Antibody directed cytotxicity
• Induction of apoptosis
• Sensitises cells to action of conventional cytotoxics
• Dose
• 375mg/m2 iv on day 1 of each chemo cycle after administration of the steroid component
• Side effects
• Infusion related reactions
• 50%, usually during the 1^st infusion (1^st 1-2hours)
• Fever, chills, rigors
• Flushing, angioedema, nausea, urticaria, fatigue, headache, tumour pain
• 10% associated with bronchospasm and hypotension
• Severe reactions are more common in patients with a high tumour burden
• Women of child bearing age need to avoid pregnacy for at least 1 year (crosses placenta and can be teratogenic)
• Cost
• £9,800/ course (8 cycles)
• Evidence
• CHOP v R-CHOP for 8 cycles in stage I, III, IV
• 399 untreated patients aged 60-80
• Primary end points event free survival
• Median follow-up 24 months
• 43% v 61% event free survival
• Death 29% v 41%
• Adverse events 74% CHOP v 79% R-CHOP
• No comparative data in younger people
• Small uncontrolled phase II study , response rate with R-CHOP was at least as good in those people aged over 60
• Cost effectivenes
• Cost per QALY £6100