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BookmarkScienceDaily (Dec. 16, 2004) — SAN DIEGO - Combining two biologic agents with chemotherapy forms a potent drug regimen that is showing promise in treating patients who have relapsed with the most common kind of leukemia, chronic lymphocytic leukemia (CLL), researchers from The University of Texas M. D. Anderson Cancer Center report at the annual meeting of the American Society of Hematology (ASH).
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The researchers combined two different monoclonal antibodies, alemtuzumab (Campath-1H) and rituximab (Rituxan) with the chemotherapy drugs cyclophosphamide and fludarabine. The combination is referred to as CFAR. Of 31 currently evaluable patients, 7 (23 percent) achieved complete remission, meaning no evidence of CLL remains, and the amount of leukemia in 11 patients (35 percent) has been reduced by at least half, says William Wierda, M.D., Ph.D., assistant professor of medicine in the Department of Leukemia.
"An overall response rate so far of 55 percent is very encouraging in this heavily pretreated population of patients that had limited treatment options," he says.
This study follows one reported by Wierda at last year's ASH meeting in which 143 less heavily pretreated patients were treated with rituximab, cyclophosphamide and fludarabine. This combination produced a response rate of 72 percent, of which 28 percent of patients achieved complete response remission. This complete remission rate was much higher than groups treated with either chemotherapy alone, or in combination.
Wierda and his group thought about adding alemtuzumab to the combination because of the synergistic activity of FCR and report that fludarabine combined with alemtuzumab had activity in patients that were resistant to both these agents. Alemtuzumab targets CD52, a protein expressed on the surface of leukemia cells. Rituximab, approved for use in follicular non-Hodgkin's lymphoma, targets CD20, also a cell surface protein on leukemia cells.
In the current trial, which is ongoing, patients have not experienced serious toxicity or early death, and Wierda expects the number of responders to increase with continued enrollment of less heavily pretreated patients. About half of the patients treated with CFAR had previously received FCR. "Had these patients been treated again with FCR,the response rate would not have reached that achieved with CFAR," he says.
