Over the last few years, several
monoclonal antibodies have been investigated in patients with B-cell lymphoid
malignancies.
Rituximab is the most important
monoclonal antibody of clinical value in these disorders.
Rituximab is an
IgG1 chimeric antibody containing murine light- and heavy-chain variable region sequences and human constant region sequences. Since approval in 1997,
rituximab has become the standard of care in follicular
B-cell lymphoma,
chronic lymphocytic leukemia (CLL) and aggressive
lymphoma when combined with
chemotherapy. Higher clinical benefits of
rituximab can be seen in patients with CLL when it is added to other chemotherapeutic agents. Several recent reports have suggested that in patients with CLL,
rituximab combined with
purine nucleoside analogs (PNAs) or PNAs and
cyclophosphamide may improve the results with acceptable toxicity, both in previously untreated and refractory/relapsed patients. The randomized, multinational Phase III study (REACH trial) has shown that
rituximab combined with
fludarabine and
cyclophosphamide (R-FC regimen) results in 10 months longer progression-free survival, and higher overall response and complete response rates than
fludarabine and
cyclophosphamide (FC regimen) in previously treated patients. The German CLL study group initiated a multicenter, multinational Phase III trial, CLL8, to evaluate the efficacy and tolerability of R-FC versus FC for the first-line treatment of patients with advanced CLL. The overall response rate was significantly higher in the R-FC arm (95%) compared with FC (88%). The complete response rate in the R-FC arm was 44% compared with 27% in the FC arm. The recently updated analysis has demonstrated longer overall survival in the R-FC group. Recent clinical observations have revealed that combinations of
rituximab with
pentostatin and
cyclophosphamide, or
cladribine and
cyclophosphamide are also highly active regimens in previously untreated CLL. In addition, the results of treatment with high-dose
methylprednisolone in combination with
rituximab in advanced CLL resistant to
fludarabine have been reported recently by several groups. However, available
therapies are only partially effective in CLL, exposing an obvious need to develop new, more specific and active drugs. Recently, several new anti-CD20
monoclonal antibodies have been developed and are now being evaluated in clinical trials.