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

Sergio Cortelazzo, Corrado Tarella, Alessandro Massimo Gianni, Marco Ladetto, A. Barbui, A. Rossi, G. Gritti, P. Corradini, Massimo Di Nicola, C. Patti, Antonino Mulè, Manuela Zanni, Valerio Zoli, Atto Billio, Andrea Piccin, Giovanni Negri, C. Castellino, Francesco Di Raimondo, Andres Ferreri, F. Benedetti & 14 others G. La Nasa, Guido Gini, L. Trentin, Maurizio Frezzato, Leonardo Flenghi, S. Falorio, Marco Chilosi, Riccardo Bruna, Valentina Tabanelli, Stefano Pileri, Arianna Masciulli, F. Delaini, Cristina Boschini, Alessandro Rambaldi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4015-4022
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number33
DOIs
Publication statusPublished - Nov 20 2016

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Lymphoma, Large B-Cell, Diffuse
Drug Therapy
Disease-Free Survival
Stem Cell Transplantation
Vincristine
Prednisone
Rituximab
Doxorubicin
Cyclophosphamide
Therapeutics
Survival
Mortality

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Randomized trial comparing R-CHOP versus high-dose sequential chemotherapy in high-risk patients with diffuse large B-cell lymphomas. / Cortelazzo, Sergio; Tarella, Corrado; Gianni, Alessandro Massimo; Ladetto, Marco; Barbui, A.; Rossi, A.; Gritti, G.; Corradini, P.; Di Nicola, Massimo; Patti, C.; Mulè, Antonino; Zanni, Manuela; Zoli, Valerio; Billio, Atto; Piccin, Andrea; Negri, Giovanni; Castellino, C.; Di Raimondo, Francesco; Ferreri, Andres; Benedetti, F.; La Nasa, G.; Gini, Guido; Trentin, L.; Frezzato, Maurizio; Flenghi, Leonardo; Falorio, S.; Chilosi, Marco; Bruna, Riccardo; Tabanelli, Valentina; Pileri, Stefano; Masciulli, Arianna; Delaini, F.; Boschini, Cristina; Rambaldi, Alessandro.

In: Journal of Clinical Oncology, Vol. 34, No. 33, 20.11.2016, p. 4015-4022.

Research output: Contribution to journalArticle

Cortelazzo, S, Tarella, C, Gianni, AM, Ladetto, M, Barbui, A, Rossi, A, Gritti, G, Corradini, P, Di Nicola, M, Patti, C, Mulè, A, Zanni, M, Zoli, V, Billio, A, Piccin, A, Negri, G, Castellino, C, Di Raimondo, F, Ferreri, A, 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 2016, 'Randomized trial comparing R-CHOP versus high-dose sequential chemotherapy in high-risk patients with diffuse large B-cell lymphomas', Journal of Clinical Oncology, vol. 34, no. 33, pp. 4015-4022. https://doi.org/10.1200/JCO.2016.67.2980
Cortelazzo, Sergio ; Tarella, Corrado ; Gianni, Alessandro Massimo ; Ladetto, Marco ; Barbui, A. ; Rossi, A. ; Gritti, G. ; Corradini, P. ; Di Nicola, Massimo ; Patti, C. ; Mulè, Antonino ; Zanni, Manuela ; Zoli, Valerio ; Billio, Atto ; Piccin, Andrea ; Negri, Giovanni ; Castellino, C. ; Di Raimondo, Francesco ; Ferreri, Andres ; Benedetti, F. ; La Nasa, G. ; Gini, Guido ; Trentin, L. ; Frezzato, Maurizio ; Flenghi, Leonardo ; Falorio, S. ; Chilosi, Marco ; Bruna, Riccardo ; Tabanelli, Valentina ; Pileri, Stefano ; Masciulli, Arianna ; Delaini, F. ; Boschini, Cristina ; Rambaldi, Alessandro. / Randomized trial comparing R-CHOP versus high-dose sequential chemotherapy in high-risk patients with diffuse large B-cell lymphomas. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 33. pp. 4015-4022.
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title = "Randomized trial comparing R-CHOP versus high-dose sequential chemotherapy in high-risk patients with diffuse large B-cell lymphomas",
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.",
author = "Sergio Cortelazzo and Corrado Tarella and Gianni, {Alessandro Massimo} and Marco Ladetto and A. Barbui and A. Rossi and G. Gritti and P. Corradini and {Di Nicola}, Massimo and C. Patti and Antonino Mul{\`e} and Manuela Zanni and Valerio Zoli and Atto Billio and Andrea Piccin and Giovanni Negri and C. Castellino and {Di Raimondo}, Francesco and Andres Ferreri and F. Benedetti and {La Nasa}, G. and Guido Gini and L. Trentin and Maurizio Frezzato and Leonardo Flenghi and S. Falorio and Marco Chilosi and Riccardo Bruna and Valentina Tabanelli and Stefano Pileri and Arianna Masciulli and F. Delaini and Cristina Boschini and Alessandro Rambaldi",
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doi = "10.1200/JCO.2016.67.2980",
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volume = "34",
pages = "4015--4022",
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TY - JOUR

T1 - Randomized trial comparing R-CHOP versus high-dose sequential chemotherapy in high-risk patients with diffuse large B-cell lymphomas

AU - Cortelazzo, Sergio

AU - Tarella, Corrado

AU - Gianni, Alessandro Massimo

AU - Ladetto, Marco

AU - Barbui, A.

AU - Rossi, A.

AU - Gritti, G.

AU - Corradini, P.

AU - Di Nicola, Massimo

AU - Patti, C.

AU - Mulè, Antonino

AU - Zanni, Manuela

AU - Zoli, Valerio

AU - Billio, Atto

AU - Piccin, Andrea

AU - Negri, Giovanni

AU - Castellino, C.

AU - Di Raimondo, Francesco

AU - Ferreri, Andres

AU - Benedetti, F.

AU - La Nasa, G.

AU - Gini, Guido

AU - Trentin, L.

AU - Frezzato, Maurizio

AU - Flenghi, Leonardo

AU - Falorio, S.

AU - Chilosi, Marco

AU - Bruna, Riccardo

AU - Tabanelli, Valentina

AU - Pileri, Stefano

AU - Masciulli, Arianna

AU - Delaini, F.

AU - Boschini, Cristina

AU - Rambaldi, Alessandro

PY - 2016/11/20

Y1 - 2016/11/20

N2 - 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.

AB - 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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U2 - 10.1200/JCO.2016.67.2980

DO - 10.1200/JCO.2016.67.2980

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JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

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