Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial

Background The outcome of diff use large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18–59 years, the potential survival benefi t provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab.
Methods We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclo phosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18–59 years with untreated diff use large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of effi cacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595.
Findings One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75–86) in the R-ACVBP group and 67% (59–73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38–0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81–91] vs 73% [66–79]; HR 0·48 [0·30–0·76]; p=0·0015) and overall survival (92% [87–95] vs 84% [77–89]; HR 0·44 [0·28–0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3–4 haematological toxic eff ects were more common in the R-ACVBP group, with a higher proportion of patients experiencing
a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]).
Interpretation Compared with standard R-CHOP, inten sifi ed immunochemotherapy with R-ACVBP signifi cantly improves survival of patients aged 18–59 years with diff use large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic eff ects of the intensive regimen were raised but manageable.
Funding Groupe d’Etudes des Lymphomes de l’Adulte and Amgen.