Rituximab combination therapy improves progression-free survival in patients with CLL
Colgne/Basel - Addition of Roche's monoclonal anti-CD20 antibody rituximab to first-line chemotherapy with fludarabine plus cyclophosphamide has improved therapy outcome in patients with chronic lymphocytic leukaemia (CLL) compared with standard chemotherapy alone (Lancet, Cancer Special Issue). In a Phase III trial, 817 therapy-native patients with CLL, that were assigned in a one-to-one ratio to recieve 6 courses of intravenous fludarabine (25 mg/m3.d) and cyclophosphamide (250 mg/m3.d) for the first 3 days of a 28 day treatment course with or without rituximab (375 mg/m3,d on day 0 of 1st course, and 500 mg/m3 on day 1 of the following 5 courses). While 65% of the rituximab group were progression-free at 3 years after randomisation compared to 45% in the chemotherapy only group, the researchers headed by Professor Michael Hallek at University of Cologne observed no significant benefit in overall survival. 87% vs 83% were alive at that point in time. However the risk for leukocytoopenia was 24% vs 12% in the rituximab vs chemotherapy-only group. Additionally, the risk for severe (grade 3-4) neutropenia was higher on rituximab (136 vs 83 patients). CLL is the second most common type of leukaemia. Typically, chemotherapy has been used to treat CLL, but there is currently no treatment available that improves overall survival. Interestingly, improvement in outcome was not uniform across all clinical and genetic subgroups. In particular, patients with chromosome 17p deletion (or p53 dysfunctional CLL) had a poor response, with fewer than 5% achieving complete remission even with chemoimmunotherapy treatment. By contrast, the rate of complete remission increased by more than three times with chemoimmunotherapy in patients with chromosome 11q deletion, a group considered to have a poor prognosis.