title: 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.
abstract: BACKGROUND
  The outcome of diffuse 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 benefit 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, cyclophosphamide, 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 diffuse large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595.
  
  
  RESULTS
  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 effects 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]).
  
  
  CONCLUSIONS
  Compared with standard R-CHOP, intensified immunochemotherapy with R-ACVBP significantly improves survival of patients aged 18-59 years with diffuse large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic effects of the intensive regimen were raised but manageable.
  
  
  BACKGROUND
  Groupe d'Etudes des Lymphomes de l'Adulte and Amgen.
authors: Centre Hospitalier Universitaire de Toulouse, France.
authors: Christian
authors: C
authors: Récher
authors: Bertrand
authors: B
authors: Coiffier
authors: Corinne
authors: C
authors: Haioun
authors: Thierry Jo
authors: TJ
authors: Molina
authors: Christophe
authors: C
authors: Fermé
authors: Olivier
authors: O
authors: Casasnovas
authors: Catherine
authors: C
authors: Thiéblemont
authors: André
authors: A
authors: Bosly
authors: Guy
authors: G
authors: Laurent
authors: Franck
authors: F
authors: Morschhauser
authors: Hervé
authors: H
authors: Ghesquières
authors: Fabrice
authors: F
authors: Jardin
authors: Serge
authors: S
authors: Bologna
authors: Christophe
authors: C
authors: Fruchart
authors: Bernadette
authors: B
authors: Corront
authors: Jean
authors: J
authors: Gabarre
authors: Christophe
authors: C
authors: Bonnet
authors: Maud
authors: M
authors: Janvier
authors: Danielle
authors: D
authors: Canioni
authors: Jean-Philippe
authors: JP
authors: Jais
authors: Gilles
authors: G
authors: Salles
authors: Hervé
authors: H
authors: Tilly
mesh_terms: D000293:Adolescent; D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011239:Prednisolone; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D018570:Risk Assessment; D000069283:Rituximab; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine; D014751:Vindesine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001761:Bleomycin; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D014751:Vindesine; D011241:Prednisone