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.
Details
Serval ID
serval:BIB_EE503740B7C7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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.
Journal
Lancet
Working group(s)
Groupe d'Etude des Lymphomes de l'Adulte
Contributor(s)
Van Hoof A., Van Eygen K., Lamperz S., André M., Bonnet C., Fillet G., Boulet D., Maerevoet M., Van Den Neste E., Bosly A., Demuynck H., Straetmans N., Mathieux V., Mineur P., Pierre P., Bron D., Kentos A., Zachee P., Fruchart C., Marit G., Jardin F., Tilly H., Corront B., Martin C., Lepeu G., Orfeuvre H., Salles B., Blanc M., Al Jassem L., Wetterwald M., Kulekci C., Vallantin X., Soussain C., Eisenmann JC., Morvan F., Azagury M., Devidas A., Morschhauser F., Bologna S., Feugier P., Macro M., Casanovas O., Bordessoule D., Karsenti JM., Mounier N., Jourdan E., Herbrecht R., Laurent G., Récher C., Coiffier B., Salles G., Delmer A., Anglaret B., Ghesquiéres H., Sebban C., Janvier M., Fabbro M., Flesch M., Castaigne S., Fenaux P., Besson C., Mosser L., Christian B., Gabarre J., Maréchal F., De Revel T., Belhadj K., Haioun C., Marjanovic Z., Fain O., Delarue R., Sebahoun G., Audhuy B., Aoudjhane M., Gisselbrecht C., Thièblemont C., Rose C., Fleck E., Decaudin D., Colin P., Fermé C., Ribrag V., Fitoussi O., Ketterer N.
ISSN
1474-547X (Electronic)
ISSN-L
0140-6736
Publication state
Published
Issued date
2011
Volume
378
Number
9806
Pages
1858-1867
Language
english
Notes
Publication types: Clinical Trial, Phase III ; Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
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.
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.
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.
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.
Keywords
Adolescent, Adult, Antibodies, Monoclonal, Murine-Derived/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Bleomycin/administration & dosage, Bleomycin/adverse effects, Cyclophosphamide/administration & dosage, Cyclophosphamide/adverse effects, Disease-Free Survival, Dose-Response Relationship, Drug, Doxorubicin/administration & dosage, Doxorubicin/adverse effects, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Lymphoma, Large B-Cell, Diffuse/diagnosis, Lymphoma, Large B-Cell, Diffuse/drug therapy, Male, Maximum Tolerated Dose, Middle Aged, Prednisolone, Prednisone/administration & dosage, Prednisone/adverse effects, Prospective Studies, Risk Assessment, Severity of Illness Index, Survival Analysis, Treatment Outcome, Vincristine, Vindesine/administration & dosage, Vindesine/adverse effects, Young Adult
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07/02/2012 14:46
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20/08/2019 17:15
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