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, 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); Sezer, O; Ordemann, R; Behringer, D; Brossart, P; Fritsch, G; Pflüger, KH; Hänel, M; Peter, N; Levknecht, C; Ehninger, G; Schlegel, F; Dührsen, U; Weidmann, E; Kiehl, M; Giagounidis, A; Trümper, L; Dölken, G; Lindemann, HW; Appel, T; Schmoll, HJ; Bokemeyer, C; Salwender, H; Schmitz, N; Glass, B; Nickelsen, M; Balleisen, H; Kirchner, H; Kirchner, H; Dreger, P; Tron, V; Kaiser, U; Pfreundschuh, M; Kiehl, M; Bentz, M; Kneba, M; Borchmann, P; Frieling, T; Hartmann, F; Fetscher, S; Brosig, B; Hoffmann, J; Fischer, T; Hofmann, WK; Gräven, U; Schmidt, C; Karthaus, M; Peschel, C; Mesters, R; Falge, C; Müller, H; Gaska, T; Maschmeyer, G; Freund, M; Potratz, J; Hähling, D; Gassmann, W; Kölbel, CB; Clemens, M; Kubin, TW; Viardot, A; Frickhofen, N     «

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); Sezer, O; Ordemann, R; Behringer, D; Brossart, P; Fritsch, G; Pflüger, KH; Hänel, M; Peter, N; Levknecht, C; Ehninger, G; Schlegel, F; Dührsen, U; Weidmann, E; Kiehl, M; Giagounidis, A; Trümper, L; Dölken, G; Lindemann, HW; Appel, T; Schmoll,...     »

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.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 NCT00129090.136 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.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.Deutsche Krebshilfe.     «

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.We did an open-label, randomised tr...     »