Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% (P = 83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = 12), or overall survival (74% v 77%, respectively; P = 64). Significantly higher hematologic toxicity (P<.001) and more infectious complications (P < 001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.

Randomized trial comparing R-CHOP versus high-dose sequential chemotherapy in high-risk patients with diffuse large B-cell lymphomas

Tarella C.;Gianni A. M.;Ladetto M.;Rossi A.;Zanni M.;Zoli V.;Negri G.;Trentin L.;Bruna R.;Pileri S.;Masciulli A.;
2016-01-01

Abstract

Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% (P = 83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = 12), or overall survival (74% v 77%, respectively; P = 64). Significantly higher hematologic toxicity (P<.001) and more infectious complications (P < 001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.
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http://ascopubs.org/doi/pdf/10.1200/JCO.2016.67.2980
Adolescent; Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prednisone; Rituximab; Stem Cell Transplantation; Treatment Outcome; Vincristine; Young Adult
Cortelazzo S.; Tarella C.; Gianni A.M.; Ladetto M.; Barbui A.M.; Rossi A.; Gritti G.; Corradini P.; Di Nicola M.; Patti C.; Mule A.; Zanni M.; Zoli V.; Billio A.; Piccin A.; Negri G.; Castellino C.; Di Raimondo F.; Ferreri A.J.M.; Benedetti F.; La Nasa G.; Gini G.; Trentin L.; Frezzato M.; Flenghi L.; Falorio S.; Chilosi M.; Bruna R.; Tabanelli V.; Pileri S.; Masciulli A.; Delaini F.; Boschini C.; Rambaldi A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1732712
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