title: Frontline low-dose alemtuzumab with fludarabine and cyclophosphamide prolongs progression-free survival in high-risk CLL.
abstract: 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.
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark;
authors.forename: Christian H
authors.initials: CH
authors.lastname: Geisler
authors.affiliation: Department of Hematology, Erasmus Medisch Centrum, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands;
authors.forename: Mars B
authors.initials: MB
authors.lastname: van T' Veer
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark;
authors.forename: Jesper
authors.initials: J
authors.lastname: Jurlander
authors.affiliation: Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland, on behalf of the Polish Lymphoma Research Group Centers;
authors.forename: Jan
authors.initials: J
authors.lastname: Walewski
authors.affiliation: Department of Hematology, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway;
authors.forename: Geir
authors.initials: G
authors.lastname: Tjønnfjord
authors.affiliation: Department of Hematology, Turku University Central Hospital, Finland;
authors.forename: Maija
authors.initials: M
authors.lastname: Itälä Remes
authors.affiliation: Department of Hematology Karolinska University Hospital, Stockholm, Sweden;
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.affiliation: Department of Hematology, University Hospital Kralovske Vinohrady, Prague, Czech Republic;
authors.forename: Tomas
authors.initials: T
authors.lastname: Kozak
authors.affiliation: Department of Hematology, Hadassah University Hospital and Hebrew University Medical School, Jerusalem, Israel;
authors.forename: Aaron
authors.initials: A
authors.lastname: Polliack
authors.affiliation: Department of Hematology, ZNA Stuivenberg, Antwerp, Belgium;
authors.forename: Ka Lung
authors.initials: KL
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, Meander Medical Center, Amersfoort, The Netherlands;
authors.forename: Shulamiet
authors.initials: S
authors.lastname: Wittebol
authors.affiliation: The Haemato Oncology Foundation for Adults in The Netherlands (HOVON) Data Centre, Erasmus Medisch Centrum, Clinical Trial Center, Rotterdam, The Netherlands; and.
authors.forename: Martine C J
authors.initials: MC
authors.lastname: Abrahamse-Testroote
authors.affiliation: Department of Hematology, Erasmus Medisch Centrum, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands;
authors.forename: Jeanette
authors.initials: J
authors.lastname: Doorduijn
authors.affiliation: The Haemato Oncology Foundation for Adults in The Netherlands (HOVON) Data Centre, Erasmus Medisch Centrum, Clinical Trial Center, Rotterdam, The Netherlands; and.
authors.forename: Wendimagegn
authors.initials: W
authors.lastname: Ghidey Alemayehu
authors.affiliation: Department of Hematology, Academisch Medisch Centrum, Amsterdam, The Netherlands.
authors.forename: Marinus H J
authors.initials: MH
authors.lastname: van Oers
mesh_terms: D000368:Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine