title: CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group.
abstract: BACKGROUND
  The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma. Extended follow-up was needed to establish long-term effects.
  
  
  METHODS
  In the randomised open-label MInT study, patients from 18 countries (aged 18-60 years with none or one risk factor according to the age-adjusted International Prognostic Index [IPI], stage II-IV disease or stage I disease with bulk) were randomly assigned to receive six cycles of a CHOP-like chemotherapy with or without rituximab. Bulky and extranodal sites received additional radiotherapy. Randomisation was done centrally with a computer-based tool and was stratified by centre, bulky disease, age-adjusted IPI, and chemotherapy regimen by use of a modified minimisation algorithm that incorporated a stochastic component. Patients and investigators were not masked to treatment allocation. The primary endpoint was event-free survival. Analyses were by intention to treat. This observational study is a follow-up of the MInT trial, which was stopped in 2003, and is registered at ClinicalTrials.gov, number NCT00400907.
  
  
  RESULTS
  The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab. After a median follow-up of 72 months (range 0·03-119), 6-year event-free survival was 55·8% (95% CI 50·4-60·9; 166 events) for patients assigned to chemotherapy alone and 74·3% (69·3-78·6; 98 events) for those assigned to chemotherapy plus rituximab (difference between groups 18·5%, 11·5-25·4, log-rank p<0·0001). Multivariable analyses showed that event-free survival was affected by treatment group, presence of bulky disease, and age-adjusted IPI and that overall survival was affected by treatment group and presence of bulky disease only. After chemotherapy and rituximab, a favourable subgroup (IPI=0, no bulk) could be defined from a less favourable subgroup (IPI=1 or bulk, or both; event-free survival 84·3% [95% CI 74·2-90·7] vs 71·0% [65·1-76·1], log-rank p=0·005). 18 (4·4%, 95% CI 2·6-6·9) second malignancies occurred in the chemotherapy-alone group and 16 (3·9%, 2·2-6·2) in the chemotherapy and rituximab group (Fisher's exact p=0·730).
  
  
  CONCLUSIONS
  Rituximab added to six cycles of CHOP-like chemotherapy improved long-term outcomes for young patients with good-prognosis diffuse large-B-cell lymphoma. The definition of two prognostic subgroups allows a more refined therapeutic approach to these patients than does assessment by IPI alone.
  
  
  BACKGROUND
  Hoffmann-La Roche.
authors.affiliation: Universitätsklinikum des Saarlandes, Homburg, Germany. michael.pfreundschuh@uks.eu
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Evelyn
authors.initials: E
authors.lastname: Kuhnt
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.forename: Anders
authors.initials: A
authors.lastname: Osterborg
authors.forename: Marek
authors.initials: M
authors.lastname: Trneny
authors.forename: Lois
authors.initials: L
authors.lastname: Shepherd
authors.forename: Devinder S
authors.initials: DS
authors.lastname: Gill
authors.forename: Jan
authors.initials: J
authors.lastname: Walewski
authors.forename: Ruth
authors.initials: R
authors.lastname: Pettengell
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaeger
authors.forename: Pier-Luigi
authors.initials: PL
authors.lastname: Zinzani
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.forename: Stein
authors.initials: S
authors.lastname: Kvaloy
authors.forename: Peter
authors.initials: P
authors.lastname: de Nully Brown
authors.forename: Rolf
authors.initials: R
authors.lastname: Stahel
authors.forename: Noel
authors.initials: N
authors.lastname: Milpied
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: Viola
authors.initials: V
authors.lastname: Poeschel
authors.forename: Sandra
authors.initials: S
authors.lastname: Grass
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.forename: Niels
authors.initials: N
authors.lastname: Murawski
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001315:Australia; D002170:Canada; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005060:Europe; D006801:Humans; D007557:Israel; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D012307:Risk Factors; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone