Immunochemotherapy in indolent non-Hodgkin's lymphoma

Abstract

Non-Hodgkin's lymphomas (NHLs) comprise a diverse group of lymphatic malignancies of primarily B-cell origin, which are steadily increasing in prevalence worldwide. Of these, the indolent NHLs, although initially responsive to a variety of therapeutic regimens, have a continuous relapsing nature and are essentially incurable. Consequently, novel and innovative treatments are urgently required to prolong overall survival in patients with this disease. Rituximab, a human-mouse chimeric monoclonal antibody that mobilizes host effector mechanisms to destroy B cells expressing the CD20 antigen, has proven single-agent efficacy in NHL. There is a powerful rationale for combining rituximab with conventional chemotherapeutic agents to improve the outcome in NHL. A study evaluating the efficacy of rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) immunochemotherapy has been conducted in 40 patients diagnosed with indolent NHL. The overall response rate was 95% (38 of 40 patients) and 22 patients (55%) experienced a complete response. No unexpected toxicity was observed with the combination therapy. Median time to progression is not reached after 50 months of follow-up. Using a highly sensitive polymerase chain reaction technique, it was also shown that rituximab plus CHOP resulted in the elimination of bcl-2-positive lymphoma cells. A further study assessing whether or not similar efficacy can be achieved using rituximab combined with fludarabine chemotherapy has provided very encouraging early results to date, with an initial overall response rate of 93% in 30 treated patients and a complete response rate of 80%. Clearance of bcl-2-positive cells, as observed in the CHOP study, has also been achieved in these patients. The combination of rituximab with conventional chemotherapeutic agents such as CHOP appears to be a viable treatment option for indolent NHL. Ongoing and planned studies will lead to the optimal use of rituximab for the treatment of NHL.