CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group.
BACKGROUND
The role of rituximab in combination with different CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like chemotherapy regimens in young patients with good-prognosis diffuse large-B-cell lymphoma remains to be defined. We aimed to compare CHOP-like chemotherapy and rituximab with CHOP-like chemotherapy alone in these patients.


METHODS
824 patients who were from 18 countries; aged 18-60 years; and who had no risk factors or one risk factor according to age-adjusted International Prognostic Index (IPI), stage II-IV disease, or stage I disease with bulk were enrolled. These patients were randomly assigned to six cycles of CHOP-like chemotherapy and rituximab (n=413) or to six cycles of CHOP-like chemotherapy alone (n=411). Bulky and extranodal sites received additional radiotherapy. The primary endpoint was event-free survival; secondary endpoints were response, progression under therapy, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat and per protocol. This trial is registered at http://www.clinicaltrials.gov, NCT 00064116.


RESULTS
After a median follow-up of 34 months (range 0.03-61), patients assigned chemotherapy and rituximab had increased 3-year event-free survival compared with those assigned chemotherapy alone (79% [95% CI 75-83] vs 59% [54-64]; difference between groups 20% [13-27], log-rank p<0.0001), and had increased 3-year overall survival (93% [90-95] vs 84% [80-88]; difference between groups 9% [3-13], log-rank p=0.0001). Event-free survival was affected by treatment group, presence of bulky disease, and age-adjusted IPI: after chemotherapy and rituximab, a favourable subgroup (ie, IPI=0, no bulk) could be defined from a less-favourable subgroup (ie, IPI=1 or bulk, or both). Groups did not differ in the frequency of adverse events.


CONCLUSIONS
Rituximab added to six cycles of CHOP is an effective treatment for young patients with good-prognosis diffuse large-B-cell lymphoma. The definition of two prognostic subgroups allows for a more refined therapeutic approach for these patients.
Pfreundschuh
Michael
M
University Clinic of Saarland, Homburg, Germany. michael.pfreundschuh@uniklinikum-saarland.de
Trümper
Lorenz
L
Osterborg
Anders
A
Pettengell
Ruth
R
Trneny
Marek
M
Imrie
Kevin
K
Ma
David
D
Gill
Devinder
D
Walewski
Jan
J
Zinzani
Pier-Luigi
PL
Stahel
Rolf
R
Kvaloy
Stein
S
Shpilberg
Ofer
O
Jaeger
Ulrich
U
Hansen
Mads
M
Lehtinen
Tuula
T
López-Guillermo
Armando
A
Corrado
Claudia
C
Scheliga
Adriana
A
Milpied
Noel
N
Mendila
Myriam
M
Rashford
Michelle
M
Kuhnt
Evelyn
E
Loeffler
Markus
M
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D003520:Cyclophosphamide; D018572:Disease-Free Survival; D004317:Doxorubicin; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy*; D008875:Middle Aged; D011241:Prednisone; D011379:Prognosis; D000069283:Rituximab; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone