In a randomized phase III trial among previously treated patients with relapsed or refractory chronic lymphocytic leukemia (CLL), the combination of alemtuzumab (Campath) plus fludarabine resulted in significant improvements in progression-free survival, complete response rate, and overall survival compared to patients receiving fludarabine alone. “The fludarabine plus alemtuzumab combination provides clinical benefits with an acceptable safety profile,” trial investigators reported in The Lancet Oncology.
A total of 335 patients with relapsed or refractory CLL and evidence of progressive disease that required therapy after one previous treatment for CLL were enrolled in the trial at 5 North American and 43 European centers. The patients were randomly assigned to open-label combination treatment (fludarabine at 30 mg/m2 per day and alemtuzumab at 30 mg per day on days 1–3) or to monotherapy (fludarabine at 25 mg/m2 on days 1–5). Both regimens were given intravenously for a maximum of six 28-day cycles.
Median progression-free survival for the 168 patients in the fludarabine-plus-alemtuzumab group was 23.7 months vs 16.5 months for the 167 patients in the fludarabine-only group (P = .0003). Overall median survival was not reached in the combination group and was 52.9 months in the fludarabine-alone group. The complete response rate was 13% among patients receiving alemtuzumab and fludarabine vs 4% among patients receiving fludarabine alone.
All-cause adverse events occurred in 98% of patients receiving combination treatment and 90% of patients receiving fludarabine alone. Patients in the fludarabine-plus-alemtuzumab group had more cytomegalovirus events (14% vs < 1% in the monotherapy group). Grade 3 or 4 toxicities occurring in the combination treatment and monotherapy groups were leukopenia (74% vs 34%), lymphopenia (94% vs 33%), neutropenia (59% vs 68%), thrombocytopenia (11% vs 17%), and anemia (9% vs 17%). Despite the difference in the incidence of grade 3/4 adverse events, the percentage of patients who discontinued treatment or died during treatment was similar in the two groups, the authors noted.
“For second-line therapy, the fludarabine-plus-alemtuzumab regimen has several potential advantages,” the researchers stated. “First, unlike fludarabine plus cyclophosphamide and fludarabine plus cyclophosphamide plus rituximab [Rituxan], the fludarabine-plus-alemtuzumab regimen spares patients from additional exposure to alkylating drugs, which theoretically might be associated with serious early and late toxicities.” Other potential advantages are reduced doses of each drug and a more convenient dosing schedule.
“This combination might become an important additional treatment option for patients with relapsed or refractory CLL,” the authors concluded. ■
Elter E, et al: Lancet Oncology 12:1204-1213, 2011.