Rituximab therapy of patients with B-cell chronic lymphocytic leukemia

Rituximab (IDEC-C2B8) is a chimeric antibody that binds to the B-cell surfa ce antigen CD20. Rituximab has significant activity in follicular non-Hodgk in lymphomas. Much less is known about the effects in chronic lymphocytic l eukemia (CLL). We have initiated a phase 11 trial to evaluate the efficacy and safety of rituximab in patients with CD20(+) pretreated CLL. To avoid t he rituximab-associated toxicity, we restricted the tumor cell load, as mea sured by the number of circulating lymphocytes and the spleen size, in the first 2 cohorts of patients included In the study. Patients received 4 intr avenous infusions of 375 mg/m(2) once a week over a period of 1 month. Of t he 28 patients evaluable for response, 7 patients showed a partial remissio n (National Cancer Institute criteria) lasting for a median of 20 weeks, wi th 1 patient still in remission after 71 weeks. Based on lymphocyte counts only, we found at least a 50% reduction of lymphocyte counts lasting for at least 4 weeks in 13 (45%) of 29 patients. Fifteen patients from 3 institut ions were monitored for the immunophenotype profile of lymphocyte subsets. The number of CD5(+)CD20(+) cells decreased significantly and remained low until day 28 after therapy. T-cell counts were not affected. With the excep tion of one rituximab-related death, adverse events in the remaining patien ts were mild. The results suggest that rituximab has clinical activity in p retreated patients with B-CLL. Toxicity is tolerable. Response duration aft er withdrawal of rituximab is rather short. Therefore, other modes of appli cation and the combination with other agents need to be tested. (C) 2001 by The American Society of Hematology.