Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Mabthera (Roche Products)
10 mg/mL in 10 mL and 50 mL vials
Approved indication: lymphoma
AMH Section 14
The idea of treating tumours with antibodies to the cancer cells is appealing. Some lymphomas may be suitable for such immunotherapy because of their cell surface markers. For example, non-Hodgkin's B-cell lymphomas have specific surface antigens. Rituximab is a genetically engineered monoclonal antibody against the CD20 antigen on the B lymphocytes.
Rituximab is thought to act by binding to the CD20 antigen. This leads to thelysis of the B lymphocytes. There is a marked decline in the number ofB cells in the peripheral blood soon after the first dose.
Although the prognosis for patients with non-Hodgkin's lymphoma is worse than for those with Hodgkin's disease, it has improved with chemotherapy. Unfortunately, some patients will be refractory to treatment and others will relapse. Some of these patients may benefit from rituximab.
The main study of rituximab involved 166 patients given 4 doses at weekly intervals. This resulted in a complete response in 10 patients and a partial response in 70 patients. The median time for patients to respond was 50 days and the highest response rate was seen in patients who had previously had a nautologous bone marrow transplant.
Rituximab is diluted and then infused slowly. Its pharmacokinetics probably resemble those of immunoglobulins. After the fourth infusion of a course, the half-life is 190 hours and rituximab will be detectable for 3-6 months after treatment.
Some adverse effects are the predictable result of infusing an antibody containing human protein e.g. hypersensitivity reactions. The majority of patients develop fevers and chills during the first infusion. Patients may complain of nausea, itching, weakness and headache. Hypotension and bronchospasm can develop. If these adverse effects occur, the infusion should be slowed or stopped and supportive care given e.g. intravenous saline. The incidence of infusion-related events declines from 80% during the first infusion to 40% with subsequent infusions.
As the CD20 antigen is found on normal as well as malignant lymphocytes, a fall in lymphocytes is to be expected. It is unclear if this significantly alters the risk of infection. The lymphocytes begin to recover 6 months after treatment and usually return to normal during the next 6 months. Although theCD20 antigen is not found on stem cells or plasma cells, severe haematological abnormalities can occur. These include neutropenia, anaemia and thrombocytopenia.
The studies of rituximab have been uncontrolled, but its efficacy is probably similar to that of cladribine or fludarabine. While rituximab increases the therapeutic options for patients with relapsed or refractory low grade non-Hodgkin's lymphomas, its precise role in treatment needs clarification.