Journal Article

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

Morschhauser, Franck, Tilly, Hervé, Corront, Bernadette, Coiffier, Bertrand, Ghesquières, Hervé, Canioni, Danielle, Bologna, Serge, Fermé, Christophe, Thiéblemont, Catherine, Bonnet, Christophe, Salles, Gilles, Bosly, André, Jardin, Fabrice, Jais, Jean-Philippe, Haioun, Corinne, Fruchart, Christophe, Récher, Christian, Janvier, Maud, Molina, Thierry Jo, Casasnovas, Olivier, Laurent, Guy, Gabarre, Jean

2011

Overview

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. 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. 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]). 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. Groupe d'Etudes des Lymphomes de l'Adulte and Amgen.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited,Lancet Publishing Group
• Subject: Adolescent / Adult / Antibodies, Monoclonal, Murine-Derived - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - adverse effects / B-cell lymphoma / B-lymphocytes / Biological and medical sciences / Bleomycin / Bleomycin - administration & dosage / Bleomycin - adverse effects / CD20 antigen / Chemotherapy / Clinical medicine / Clinical trials / Cyclophosphamide / Cyclophosphamide - administration & dosage / Cyclophosphamide - adverse effects / Dehydrogenases / Disease-Free Survival / Dose-Response Relationship, Drug / Doxorubicin / Doxorubicin - administration & dosage / Doxorubicin - adverse effects / Drug Administration Schedule / Drug dosages / drug therapy / Evidence-based medicine / Female / Follow-Up Studies / General aspects / Grants / Hematologic and hematopoietic diseases / Hematology / Hepatitis / Human health sciences / Humans / Hématologie / Immunotherapy / Internal Medicine / International standardization / Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis / Lymphocytes B / Lymphoma / Lymphoma, Large B-Cell, Diffuse - diagnosis / Lymphoma, Large B-Cell, Diffuse - drug therapy / Lymphoma, Large B-Cell, Diffuse - mortality / Male / Maximum Tolerated Dose / Medical sciences / Middle Aged / Monoclonal antibodies / Motivation / Neutropenia / Patients / Population studies / Prednisolone / Prednisone / Prednisone - administration & dosage / Prednisone - adverse effects / Prospective Studies / Public speaking / Randomization / risk / Risk Assessment / Rituximab / Sciences de la santé humaine / Severity of Illness Index / Side effects / Survival / Survival Analysis / Targeted cancer therapy / Toxicity / Treatment Outcome / Tumors / Vincristine / Vindesine - administration & dosage / Vindesine - adverse effects / Young Adult