Geisler, Christian H4; van T' Veer, Mars B3; Jurlander, Jesper3; Walewski, Jan3; Tjønnfjord, Geir3; Itälä Remes, Maija3; Kimby, Eva3; Kozak, Tomas3; Polliack, Aaron3; Wu, Ka Lung3; Wittebol, Shulamiet3; Abrahamse-Testroote, Martine C J3; Doorduijn, Jeanette3; Ghidey Alemayehu, Wendimagegn3; van Oers, Marinus H J3
1 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 Section of Surgery and Internal Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Section of Surgery and Internal Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
The randomized Haemato Oncology Foundation for Adults in The Netherlands 68 phase 3 trial compared front-line chemotherapy with chemotherapy plus the CD52 monoclonal antibody alemtuzumab for high-risk chronic lymphocytic leukemia, defined as at least 1 of the following: unmutated immunoglobulin heavy chain genes, deletion 17p or 11q, or trisomy 12. Fit patients were randomized to receive either 6 28-day cycles of oral FC chemotherapy (days 1 through 3: fludarabine 40 mg/m(2) per day and cyclophosphamide 250 mg/m(2) per day: n = 139) or FC plus subcutaneous alemtuzumab 30 mg day 1 (FCA, n = 133). FCA prolonged the primary end point, progression-free survival (3-year progression-free survival 53 vs 37%, P = .01), but not the secondary end point, overall survival (OS). However, a post hoc analysis showed that FCA increased OS in patients younger than 65 years (3-year OS 85% vs 76%, P = .035). FCA also increased the overall response rate (88 vs 78%, P = .036), and the bone marrow minimal residual disease-negative complete remission rate (64% vs 43%, P = .016). Opportunistic infections were more frequent following FCA, but without an increase in treatment related mortality (FCA: 3.8%, FC: 4.3%). FCA improves progression-free survival in high-risk chronic lymphocytic leukemia. As anticipated, FCA is more immunosuppressive than FC, but with due vigilance, does not lead to a higher treatment-related mortality. This study was registered at www.trialregister.nl as trial no. NTR529.