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)

Norbert Schmitz; Maike Nickelsen; Marita Ziepert; Mathias Haenel; Peter Borchmann; Christian Schmidt; Andreas Viardot; Martin Bentz; Norma Peter; Gerhard Ehninger; Gottfried Doelken; Christian Ruebe; Lorenz Truemper; Andreas Rosenwald; Michael Pfreundschuh; Markus Loeffler; Bertram Glass; German High-Grade Lymphoma Study Group (DSHNHL); Carsten Bokemeyer

doi:10.1016/S1470-2045(12)70481-3

Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma

Standard

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, Vol. 13, No. 12, 01.12.2012, p. 1250-9.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schmitz, N, Nickelsen, M, Ziepert, M, Haenel, M, Borchmann, P, Schmidt, C, Viardot, A, Bentz, M, Peter, N, Ehninger, G, Doelken, G, Ruebe, C, Truemper, L, Rosenwald, A, Pfreundschuh, M, Loeffler, M, Glass, B, German High-Grade Lymphoma Study Group (DSHNHL) & Bokemeyer, C 2012, '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)', LANCET ONCOL, vol. 13, no. 12, pp. 1250-9. https://doi.org/10.1016/S1470-2045(12)70481-3

APA

Schmitz, N., Nickelsen, M., Ziepert, M., Haenel, M., Borchmann, P., Schmidt, C., Viardot, A., Bentz, M., Peter, N., Ehninger, G., Doelken, G., Ruebe, C., Truemper, L., Rosenwald, A., Pfreundschuh, M., Loeffler, M., Glass, B., German High-Grade Lymphoma Study Group (DSHNHL), & Bokemeyer, C. (2012). 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). LANCET ONCOL, 13(12), 1250-9. https://doi.org/10.1016/S1470-2045(12)70481-3

Vancouver

Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C et al. 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). LANCET ONCOL. 2012 Dec 1;13(12):1250-9. https://doi.org/10.1016/S1470-2045(12)70481-3

Bibtex

@article{b7d987085bfa4ff49f0427db1de085db,

title = "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)",

abstract = "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.",

keywords = "Adolescent, Adult, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols, Cyclophosphamide, Doxorubicin, Etoposide, Female, Humans, Lymphoma, B-Cell, Male, Middle Aged, Prednisolone, Vincristine, Young Adult",

author = "Norbert Schmitz and Maike Nickelsen and Marita Ziepert and Mathias Haenel and Peter Borchmann and Christian Schmidt and Andreas Viardot and Martin Bentz and Norma Peter and Gerhard Ehninger and Gottfried Doelken and Christian Ruebe and Lorenz Truemper and Andreas Rosenwald and Michael Pfreundschuh and Markus Loeffler and Bertram Glass and {German High-Grade Lymphoma Study Group (DSHNHL)} and Carsten Bokemeyer",

year = "2012",

month = dec,

day = "1",

doi = "10.1016/S1470-2045(12)70481-3",

language = "English",

volume = "13",

pages = "1250--9",

journal = "LANCET ONCOL",

issn = "1470-2045",

publisher = "Lancet Publishing Group",

number = "12",

}

RIS

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

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 -