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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Deutsche Krebshilfe.
authors.affiliation: Asklepios Hospital St Georg, Hamburg, Germany. n.schmitz@asklepios.com
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.forename: Maike
authors.initials: M
authors.lastname: Nickelsen
authors.forename: Marita
authors.initials: M
authors.lastname: Ziepert
authors.forename: Mathias
authors.initials: M
authors.lastname: Haenel
authors.forename: Peter
authors.initials: P
authors.lastname: Borchmann
authors.forename: Christian
authors.initials: C
authors.lastname: Schmidt
authors.forename: Andreas
authors.initials: A
authors.lastname: Viardot
authors.forename: Martin
authors.initials: M
authors.lastname: Bentz
authors.forename: Norma
authors.initials: N
authors.lastname: Peter
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Gottfried
authors.initials: G
authors.lastname: Doelken
authors.forename: Christian
authors.initials: C
authors.lastname: Ruebe
authors.forename: Lorenz
authors.initials: L
authors.lastname: Truemper
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.forename: Bertram
authors.initials: B
authors.lastname: Glass
mesh_terms: D000293:Adolescent; D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage; D000069283:Rituximab; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone