Rituximab and other emerging monoclonal antibody therapies for lymphoma

The recent approval of rituximab, gemtuzumab ozogamicin, alemtuzumab and ibritumomab tiuxetan by the FDA in the US revealed clear evidence that monoclonal antibodies (mAbs) have significant roles in the current treatment of haematologic malignancies. Among the mAbs under clinical development, anti-CD20 mAbs have been most extensively investigated and have shown definitive clinical efficacy. Rituximab is a genetically engineered chimeric anti-CD20 mAb, with mouse variable and human constant regions. Consecutive clinical trials conducted in the US, Europe and Japan have revealed that rituximab is a highly effective agent with acceptable toxicities against indolent and aggressive B cell non-Hodgkin's lymphomas (B-NHLs) as a single agent and in combination with cytotoxic drugs. A recent French Phase III study in elderly patients with untreated aggressive B-NHL suggested that the addition of rituximab to standard CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy increases the complete response rate and prolongs event-free and overall survival. Lymphoma cells are inherently sensitive to radiation. The aim of radioimmunotherapy is to use the mAb to target radiation to lymphoma tissue while minimising toxicity to normal cells. The clinical trials of 90Y ibritumomab tiuxetan and (131)I tositumomab showed they have definitive efficacy in relapsed indolent B-NHL with acceptable toxicities. A recent comparative study in relapsed indolent B-NHL showed that 90Y ibritumomab tiuxetan produces higher response rates than rituximab. In addition, BL22, a recombinant anti-CD22 immunotoxin, showed significant efficacy in patients with chemotherapy-resistant hairy cell leukaemia. MAbs will have significant roles in the treatment of lymphoid malignancies in the future.