Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial.
We investigated rituximab maintenance therapy in patients with diffuse large B-cell lymphoma (n=662) or follicular lymphoma grade 3b (n=21) in first complete remission. Patients were randomized to rituximab maintenance (n=338) or observation (n=345). At a median follow-up of 45 months, the event-free survival rate (the primary endpoint) at 3 years was 80.1% for rituximab maintenance versus 76.5% for observation. This difference was not statistically significant for the intent-to-treat population (likelihood ratio P=0.0670). The hazard ratio by treatment arm was 0.79 (95% confidence interval 0.57-1.08; P=0.1433). The secondary endpoint, progression-free survival was also not met for the whole statistical model (likelihood ratio P=0.3646). Of note, rituximab maintenance was superior to observation when treatment arms only were compared (hazard ratio: 0.62; 95% confidence interval 0.43-0.90; P=0.0120). Overall survival remained unchanged (92.0 versus 90.3%). In subgroup analysis male patients benefited from rituximab maintenance with regards to both event-free survival (84.1% versus 74.4%) (hazard ratio: 0.58; 95% confidence interval 0.36-0.94; P=0.0267) and progression-free survival (89.0% versus 77.6%) (hazard ratio: 0.45; 95% confidence interval 0.25-0.79; P=0.0058). Women had more grade 3/4 adverse events (P=0.0297) and infections (P=0.0341). Men with a low International Prognostic Index treated with rituximab had the best outcome. In summary, rituximab maintenance in first remission after R-CHOP-like treatment did not prolong event-free, progression-free or overall survival of patients with aggressive B-non-Hodgkin lymphoma. The significantly better outcome of men warrants further studies prior to the routine use of rituximab maintenance in men with low International Prognostic Index. This trial is registered under EUDRACT #2005-005187-90 and www.clinicaltrials.gov as #NCT00400478.
Medical University of Vienna, Dept. of Medicine I, Division of Hematology and Hemostaseology, Comprehensive Cancer Center, Vienna, Austria Arbeitsgemeinschaft Medikamentöse Tumortherapie, AGMT, Salzburg, Austria ulrich.jaeger@meduniwien.ac.at.
Ulrich
U
Jaeger
Institute of Hematology and Blood Transfusion, 1st Dept. of Medicine, 1st Faculty of Medicine, Charles University, General Hospital, Czech Lymphoma Study Group, Praha, Czech Republic.
Marek
M
Trneny
Medical University of Vienna, Dept. of Medicine I, Division of Hematology and Hemostaseology, Comprehensive Cancer Center, Vienna, Austria Arbeitsgemeinschaft Medikamentöse Tumortherapie, AGMT, Salzburg, Austria.
Helen
H
Melzer
Assign Data Management and Biostatistics GmbH Assign Group, Innsbruck, Austria Arbeitsgemeinschaft Medikamentöse Tumortherapie, AGMT, Salzburg, Austria.
Michael
M
Praxmarer
Dept. of Internal Medicine, Faculty of Medicine, Chiang Mai University, Thailand.
Weerasak
W
Nawarawong
Dept. of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Dina
D
Ben Yehuda
Australasian Leukaemia & Lymphoma Group, East Melbourne, Australia.
David
D
Goldstein
Clinic for Hematology, Clinical Center Serbia, Belgrade, Serbia.
Bilijana
B
Mihaljevic
Ankara University School of Medicine, Dept. of Hematology, Ankara, Turkey.
Osman
O
Ilhan
NOU, Klenova Bratislava, Slovakia.
Veronika
V
Ballova
Dept. of Internal Medicine, Sundsvall Hospital, Sweden.
Michael
M
Hedenus
Division of Hematology and Oncology, Dept. of Medicine, Taipei Veterans General Hospital, and National Yang-Ming University, Taipei, Taiwan.
Liang-Tsai
LT
Hsiao
University Medical Unit, Queen Mary Hospital, Hong Kong, China.
Wing-Yan
WY
Au
Dept. of Internal Medicine IV, Wels-Grieskirchen Hospital, Wels, Austria Arbeitsgemeinschaft Medikamentöse Tumortherapie, AGMT, Salzburg, Austria.
Sonja
S
Burgstaller
1st Medical Dept., Landesklinikum Wiener Neustadt, Austria Arbeitsgemeinschaft Medikamentöse Tumortherapie, AGMT, Salzburg, Austria.
Gerhard
G
Weidinger
3rd Medical Dept., Hanusch Hospital, Vienna, Austria Arbeitsgemeinschaft Medikamentöse Tumortherapie, AGMT, Salzburg, Austria.
Felix
F
Keil
LBI-ACR & ACR-ITR Vienna, Kaiser Franz Josef-Spital, Vienna, Austria Arbeitsgemeinschaft Medikamentöse Tumortherapie, AGMT, Salzburg, Austria.
Christian
C
Dittrich
Medical University of Vienna, Dept. of Medicine I, Division of Hematology and Hemostaseology, Comprehensive Cancer Center, Vienna, Austria Arbeitsgemeinschaft Medikamentöse Tumortherapie, AGMT, Salzburg, Austria.
Cathrin
C
Skrabs
Assign Data Management and Biostatistics GmbH Assign Group, Innsbruck, Austria Arbeitsgemeinschaft Medikamentöse Tumortherapie, AGMT, Salzburg, Austria.
Anton
A
Klingler
Institute of Pathology and Microbiology, Wilhelminenspital, Vienna, Austria.
Andreas
A
Chott
3rd Dept. of Medicine, AKH-Linz, Austria Arbeitsgemeinschaft Medikamentöse Tumortherapie, AGMT, Salzburg, Austria.
Michael A
MA
Fridrik
Dept. of Internal Medicine III, Private Medical University of Salzburg, Austria Arbeitsgemeinschaft Medikamentöse Tumortherapie, AGMT, Salzburg, Austria.
Richard
R
Greil
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D057194:Intention to Treat Analysis; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D000069283:Rituximab / Q000627:therapeutic use*; D012737:Sex Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D000069283:Rituximab