Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia.
OBJECTIVE
Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy. Promising results have previously been reported in nonrandomized studies in patients with chronic lymphocytic leukemia (CLL). This trial was designed to compare chemoimmunotherapy with chemotherapy alone in patients with previously treated CLL.


METHODS
This international, multicenter, randomized trial compared six cycles of rituximab plus fludarabine and cyclophosphamide (R-FC) with six cycles of fludarabine and cyclophosphamide alone (FC) in patients with previously treated CLL. A total of 552 patients with Binet stage A (1%), B (59%), or C (31%) disease entered the study and were randomly assigned to receive R-FC (n = 276) or FC (n = 276).


RESULTS
After a median follow-up time of 25 months, rituximab significantly improved progression-free survival in patients with previously treated CLL (hazard ratio = 0.65; P < .001; median, 30.6 months for R-FC v 20.6 months for FC). Event-free survival, response rate, complete response rate, duration of response, and time to new CLL treatment or death were also significantly improved. Although the rates of adverse events, grade 3 or 4 events, and serious adverse events were slightly higher in the R-FC arm, R-FC was generally well tolerated, with no new safety findings and no detrimental effect on quality of life.


CONCLUSIONS
R-FC significantly improved the outcome of patients with previously treated CLL.
Robak
Tadeusz
T
Department of Hematology, Medical University of Lodz, Ciolkowskiego 2, Lodz, Poland 93-510. robaktad@csk.umed.lodz.pl
Dmoszynska
Anna
A
Solal-Céligny
Philippe
P
Warzocha
Krzysztof
K
Loscertales
Javier
J
Catalano
John
J
Afanasiev
Boris V
BV
Larratt
Loree
L
Geisler
Christian H
CH
Montillo
Marco
M
Zyuzgin
Ilya
I
Ganly
Peter S
PS
Dartigeas
Caroline
C
Rosta
András
A
Maurer
Jörg
J
Mendila
Myriam
M
Saville
M Wayne
MW
Valente
Nancy
N
Wenger
Michael K
MK
Moiseev
Sergey I
SI
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D019233:Retreatment; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine