Concomitant treatment of patients with relapsed/refractory CLL using a combination of fludarabine and alemtuzumab is highly effective: Final results of a phase-II study

Abstract

6558 Background: Combined immuno-chemotherapy has given superadditive effects in different lymphoma entities, both in preclinical models and in clinical studies. In order to develop a more convenient active regimen for patients with relapsed CLL, we evaluated the combined application of fludarabine and alemtuzumab in a phase-II study. Methods: Fludarabine 30mg/m2 per day iv immediately followed by alemtuzumab 30 mg absolute dose iv was given on days 1 - 3 and repeated on day 29 for up to six cycles. Minimal residual disease (MRD) was measured by 4-color flow cytometry. Results: A total of 37 patients were included in this phase-II study at a median age of 61 years. Pretreatment consisted of fludarabine (23/36), fludarabine + rituximab (10/36), and monoclonal antibodies in 20/36. Thrombocytopenia and neutropenia were the most serious side effects detected in 30% and 26% of all cycles given (WHO III/IV). There were 5 grade III/IV infections, one of which was fatal due to e.coli sepsis in a patient with refractory disease. The overall response rate was 83% with 11 CR and 19 PR. 47% of the patients became MRD negative in peripheral blood or bone marrow. The freedom from treatment failure for responding patients is 12.8 months with the median overall survival for responding patients not reached. Based on these promising results, an ongoing phase-II study evaluates the effectivity of fludarabine, cyclophosphomide and alemtuzumab. In addition, a prospectively randomised phase-III trial has been initiated to confirm the impact of this new combination (FluCam) in CLL patients with first relapse. Conclusions: The concomitant application of fludarabine and alemtuzumab appears as a new promising approach for patients with relapsed CLL. No significant financial relationships to disclose.