Non-Hodgkin's lymphoma - epratuzumab
Non-Hodgkin's lymphoma is one of the most common forms of cancer. Lymphocytes multiply uncontrollably and collect in the lymph nodes, causing them to swell. Because these white blood cells circulate around the body, lymphomas can form in parts of the body other than the lymph nodes.
Non-Hodgkin's lymphoma is one of the most common forms of cancer. Lymphocytes multiply uncontrollably and collect in the lymph nodes, causing them to swell. Because these white blood cells circulate around the body, lymphomas can form in parts of the body other than the lymph nodes.
The B-lymphocyte specific glycoprotein CD22 has been observed in up to 99% of all cases of non-Hodgkin's lymphoma and is being investigated as a target for B-cell malignancies like NHL. The immunoglobulin is expressed on the cell surface at mature stages of B-cell differentiation and seems to play a crucial role in the development, survival and function of B-cells.
US company Immunomedics has developed the humanised monoclonal antibody epratuzumab that targets CD22. In Phase I/II trials, patients with relapsed or refractory indolent and aggressive NHL were given four weekly infusions of 120 to 1000mg/m2 of epratuzumab. No serious toxicity was seen and response rates ranged from 10% in those with aggressive disease to 29% in those with diffuse large B-cell NHL at doses of 240mg/m2 or more.1
Patients whose disease progressed after monotherapy with epratuzumab were given a second four-week course up to two years after the first; it was well tolerated and two of those six patients who had had an initial response achieved a second partial response.2
Its effectiveness in combination with rituximab in NHL patients has also been investigated. Rituximab-naive patients were given four weekly infusions of epratuzumab (360mg/m2 over 60 minutes) and rituximab (375mg/m2 over 4-6h).3 Five patients experienced a complete response. The most common adverse events were chills, nausea, fever and flushing.
A total of 65 patients with relapsed/refractory NHL were given doses of the two drugs in doses as before; once a week for four weeks in a multicentre open label trial.4 After 15 months disease progression was observed in 31% of those with indolent disease and 69% of those whose disease was aggressive.
A similar trial was carried out in patients with recurring low grade NHL.5 The four weekly infusions were well tolerated, but adverse events were experienced by 88% of the 49 patients. Peripheral B-cell counts decreased rapidly after the first infusion, which lasted for six to nine months after treatment. An objective response was experienced by 58% of patients, and those who had previously been dosed with rituximab were more likely to achieve an objective response.
Trials are continuing along with investigations into epratuzumab's use as a possible treatment for B-cell autoimmune diseases, notably systemic lupus erythematosus and Sjoegren's syndrome.