Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma
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Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma : an open-label, randomised, phase 3 trial (DSHNHL 2002-1). / Schmitz, Norbert; Nickelsen, Maike; Ziepert, Marita; Haenel, Mathias; Borchmann, Peter; Schmidt, Christian; Viardot, Andreas; Bentz, Martin; Peter, Norma; Ehninger, Gerhard; Doelken, Gottfried; Ruebe, Christian; Truemper, Lorenz; Rosenwald, Andreas; Pfreundschuh, Michael; Loeffler, Markus; Glass, Bertram; German High-Grade Lymphoma Study Group (DSHNHL) ; Bokemeyer, Carsten.
in: LANCET ONCOL, Jahrgang 13, Nr. 12, 01.12.2012, S. 1250-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma
T2 - an open-label, randomised, phase 3 trial (DSHNHL 2002-1)
AU - Schmitz, Norbert
AU - Nickelsen, Maike
AU - Ziepert, Marita
AU - Haenel, Mathias
AU - Borchmann, Peter
AU - Schmidt, Christian
AU - Viardot, Andreas
AU - Bentz, Martin
AU - Peter, Norma
AU - Ehninger, Gerhard
AU - Doelken, Gottfried
AU - Ruebe, Christian
AU - Truemper, Lorenz
AU - Rosenwald, Andreas
AU - Pfreundschuh, Michael
AU - Loeffler, Markus
AU - Glass, Bertram
AU - German High-Grade Lymphoma Study Group (DSHNHL)
AU - Bokemeyer, Carsten
N1 - Copyright © 2012 Elsevier Ltd. All rights reserved.
PY - 2012/12/1
Y1 - 2012/12/1
N2 - BACKGROUND: High-dose therapy (HDT) followed by transplantation of autologous haemopoietic stem cells is frequently done as part of first-line therapy in young patients with high-risk aggressive B-cell lymphoma. We investigated whether HDT with cytotoxic agents identical to those used for conventional therapy followed by autologous stem-cell transplantation (ASCT) improved survival outcome compared with conventional chemotherapy when rituximab was added to both modalities.METHODS: We did an open-label, randomised trial comparing conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) and rituximab (R-CHOEP-14) with dose-escalated sequential HDT and rituximab (R-MegaCHOEP) followed by repetitive ASCT in high-risk (age-adjusted International Prognostic Index [IPI] 2 or 3) patients aged 18-60 years with aggressive B-cell lymphoma. Eligible patients received radiotherapy for bulky, extranodal disease, or both. Randomisation (1:1) used the Pocock minimisation algorithm; patients were stratified by age-adjusted IPI factors, bulky disease, and centre. The primary endpoint was event-free survival. All analyses were done on the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00129090.FINDINGS: 136 patients were randomly assigned to R-CHOEP-14 and 139 to R-MegaCHOEP. 130 patients in the R-CHOEP-14 group and 132 in the R-MegaCHOEP group were included in the intention-to-treat population. After a median of 42 months (IQR 29-59), 3-year event-free survival was 69·5% (95% CI 61·3-77·7) in the R-CHOEP-14 group and 61·4% (52·8-70·0) in the R-MegaCHOEP group (p=0·14; hazard ratio 1·3, 95% CI 0·9-2·0). All 128 evaluable patients treated with R-MegaCHOEP had grade 4 leucopenia, as did 48 (58·5%) of 82 patients with documented blood counts in the R-CHOEP-14 group. All 128 evaluable patients in the R-MegaCHOEP group had grade 3-4 thrombocytopenia, as did 26 (33·8%) of 77 patients in the R-CHOEP-14 group with documented blood counts. The most important non-haematological grade 3 or 4 adverse event was infection, which occurred in 96 (75·0%) of 128 patients treated with R-MegaCHOEP and in 40 (31·3%) of 128 patients treated with R-CHOEP-14.INTERPRETATION: In young patients with high-risk aggressive B-cell lymphoma, R-MegaCHOEP was not superior to conventional R-CHOEP therapy and was associated with significantly more toxic effects. R-CHOEP-14 with or without radiotherapy remains a treatment option for these patients, with encouraging efficacy.FUNDING: Deutsche Krebshilfe.
AB - BACKGROUND: High-dose therapy (HDT) followed by transplantation of autologous haemopoietic stem cells is frequently done as part of first-line therapy in young patients with high-risk aggressive B-cell lymphoma. We investigated whether HDT with cytotoxic agents identical to those used for conventional therapy followed by autologous stem-cell transplantation (ASCT) improved survival outcome compared with conventional chemotherapy when rituximab was added to both modalities.METHODS: We did an open-label, randomised trial comparing conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) and rituximab (R-CHOEP-14) with dose-escalated sequential HDT and rituximab (R-MegaCHOEP) followed by repetitive ASCT in high-risk (age-adjusted International Prognostic Index [IPI] 2 or 3) patients aged 18-60 years with aggressive B-cell lymphoma. Eligible patients received radiotherapy for bulky, extranodal disease, or both. Randomisation (1:1) used the Pocock minimisation algorithm; patients were stratified by age-adjusted IPI factors, bulky disease, and centre. The primary endpoint was event-free survival. All analyses were done on the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00129090.FINDINGS: 136 patients were randomly assigned to R-CHOEP-14 and 139 to R-MegaCHOEP. 130 patients in the R-CHOEP-14 group and 132 in the R-MegaCHOEP group were included in the intention-to-treat population. After a median of 42 months (IQR 29-59), 3-year event-free survival was 69·5% (95% CI 61·3-77·7) in the R-CHOEP-14 group and 61·4% (52·8-70·0) in the R-MegaCHOEP group (p=0·14; hazard ratio 1·3, 95% CI 0·9-2·0). All 128 evaluable patients treated with R-MegaCHOEP had grade 4 leucopenia, as did 48 (58·5%) of 82 patients with documented blood counts in the R-CHOEP-14 group. All 128 evaluable patients in the R-MegaCHOEP group had grade 3-4 thrombocytopenia, as did 26 (33·8%) of 77 patients in the R-CHOEP-14 group with documented blood counts. The most important non-haematological grade 3 or 4 adverse event was infection, which occurred in 96 (75·0%) of 128 patients treated with R-MegaCHOEP and in 40 (31·3%) of 128 patients treated with R-CHOEP-14.INTERPRETATION: In young patients with high-risk aggressive B-cell lymphoma, R-MegaCHOEP was not superior to conventional R-CHOEP therapy and was associated with significantly more toxic effects. R-CHOEP-14 with or without radiotherapy remains a treatment option for these patients, with encouraging efficacy.FUNDING: Deutsche Krebshilfe.
KW - Adolescent
KW - Adult
KW - Antibodies, Monoclonal, Murine-Derived
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Cyclophosphamide
KW - Doxorubicin
KW - Etoposide
KW - Female
KW - Humans
KW - Lymphoma, B-Cell
KW - Male
KW - Middle Aged
KW - Prednisolone
KW - Vincristine
KW - Young Adult
U2 - 10.1016/S1470-2045(12)70481-3
DO - 10.1016/S1470-2045(12)70481-3
M3 - SCORING: Journal article
C2 - 23168367
VL - 13
SP - 1250
EP - 1259
JO - LANCET ONCOL
JF - LANCET ONCOL
SN - 1470-2045
IS - 12
ER -