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

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• 作者：Prof Christian Ré ; cher ; MD^a ; Prof Bertrand Coiffier ; MD^b ; Prof Corinne Haioun ; MD^c ; Prof Thierry Jo Molina ; MD^d ; Christophe Fermé ; MD^e ; Olivier Casasnovas ; MD^f ; Prof Catherine Thié ; blemont ; MD^g ; Prof André ; Bosly ; MD^h ; Prof Guy Laurent ; MD^a ; Franck Morschhauser ; MDⁱ ; Hervé ; Ghesquiè ; res ; MD^j ; Prof Fabrice Jardin ; MD^k ; Serge Bologna ; MD^l ; Christophe Fruchart ; MD^m ; Bernadette Corront ; MDⁿ ; Jean Gabarre ; MD^o ; Christophe Bonnet ; MD^p ; Maud Janvier ; MD^q ; Prof Danielle Canioni ; MD^r ; Jean-Philippe Jais ; MD^r ; Prof Gilles Salles ; MD^b ; Dr ; Prof Hervé ; Tilly ; MD^k ; ^{herve.tilly@rouen.fnclcc.fr} ; for the Groupe d'Etude des Lymphomes de l'Adulte
• 刊名：The Lancet
• 出版年：2011
• 出版时间：26 November-2 December, 2011
• 年：2011
• 卷：378
• 期：9806
• 页码：1858-1867
• 全文大小：1K

文摘

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Summary

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 , number .

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 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]).

Interpretation

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.

Funding

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