Excess mortality following FCCam treatment in previously untreated patients with CLL: safety and efficacy in a randomized, multicenter, phase III trial
Mené en Belgique et en France sur 165 patients atteints d'une leucémie lymphocytaire chronique, cet essai de phase III compare le rituximab et l'alemtuzumab en combinaison avec une chimiothérapie FC (fludarabine et cyclophosphamide)
A French and Belgian multicenter phase III trial was conducted in medically fit patients with untreated chronic lymphocytic leukemia (CLL). Of 178 patients enrolled in the study, 165 were randomly assigned to receive six courses of oral fludarabine and cyclophosphamide (FC) in combination with rituximab (R; 375 mg/m2 in cycle one, 500 mg/m2 in all subsequent cycles) or alemtuzumab (Cam; 30 mg subcutaneously injected on cycle days 1-3); each cycle was 28 days. Recruitment was halted prematurely because of excess toxicity; eight patients died in the FCCam group: three from lymphoma and five from infection. Overall response (OR) rates were 91% with FCR and 90% with FCCam (P=0.79). Complete remission (CR) rates were 33.75% with FCR and 19.2% with FCCam (P=0.04). Three-year progression-free survival (PFS) was 82.6% with FCR and 72.5% with FCCam (P=0.21). Three-year overall survival (OS) was similar between the two arms at 90.1% in the FCR arm and 86.4% in the FCCam arm (P=0.27).These results indicate that the FCCam regimen for the treatment of advanced CLL was not more effective than the FCR regimen and was associated with an unfavorable safety profile, representing a significant limitation of its use. This study is registered with www.ClinicalTrials.gov, number NCT00564512.