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

• Published in: The lancet oncology Vol. 12; no. 11; pp. 1013 - 1022
• Main Authors: Pfreundschuh, Michael, Kuhnt, Evelyn, Trümper, Lorenz, Österborg, Anders, Trneny, Marek, Shepherd, Lois, Gill, Devinder S, Walewski, Jan, Pettengell, Ruth, Jaeger, Ulrich, Zinzani, Pier-Luigi, Shpilberg, Ofer, Kvaloy, Stein, de Nully Brown, Peter, Stahel, Rolf, Milpied, Noel, López-Guillermo, Armando, Poeschel, Viola, Grass, Sandra, Loeffler, Markus, Murawski, Niels
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2011; Elsevier Limited
• Subjects: Adolescent; Adult; Age Factors; Antibodies, Monoclonal, Murine-Derived - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Australia; Canada; Chemotherapy; Cyclophosphamide - administration & dosage; Disease-Free Survival; Doxorubicin - administration & dosage; Doxorubicin - analogs & derivatives; Europe; Hematology, Oncology and Palliative Medicine; Humans; Israel; Kaplan-Meier Estimate; Lymphoma; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - pathology; Medical prognosis; Middle Aged; Neoplasm Staging; Prednisone - administration & dosage; Proportional Hazards Models; Radiation therapy; Radiotherapy, Adjuvant; Remission (Medicine); Risk Assessment; Risk Factors; Rituximab; Time Factors; Treatment Outcome; Vincristine - administration & dosage; Young Adult; Canada; Israel; Australia; Europe
• ISSN: 1470-2045; 1474-5488; 1474-5488
• DOI: 10.1016/S1470-2045(11)70235-2

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. 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. 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). 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. Hoffmann–La Roche.