Publication:
Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study

Issued Date

2018-11-01

Resource Type

Article

ISSN

14745488
14702045

DOI

10.1016/S1470-2045(18)30685-5

Other identifier(s)

2-s2.0-85056084577

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet Oncology. Vol.19, No.11 (2018), 1449-1458

Suggested Citation

Tadeusz Robak, Jie Jin, Halyna Pylypenko, Gregor Verhoef, Noppadol Siritanaratkul, Johannes Drach, Markus Raderer, Jiri Mayer, Juliana Pereira, Gayane Tumyan, Rumiko Okamoto, Susumu Nakahara, Peter Hu, Carlos Appiani, Sepideh Nemat, Franco Cavalli, Achiel Van Hoof, Adriana Sheliga, Adriana Teixeira, Akihiro Tomita, Albert Oriol Rocafiguera, Alexander Suvorov, Alexy Kuzmin, Ali Khojasteh, Amel Mezlini, Anatoly Golenkov, Andre Bosly, Andrew Belch, Ann Van De Velde, Árpád Illes, Ashis Mukhopadhyay, Balkis Meddeb, Bernard De Prijck, Bernardo Garichochea, Bulent Undar, Caballero Gabarrón, Carmen Cao, Carmino Souza, Charles Farber, Cheol Won Suh, Cristina Ileana Burcoveanu, Cristina Ligia Cebotaru, Cristina Ligia Truica, Dai Maruyama, David Belada, Dina Ben Yehuda, Dmitry Udovitsa, Dolores, Enrica Morra, Ernst Späth-Schwalbe, Eva Gonzalez-Barca, Evgenii Osmanov, Francisco Javier Capote, Fritz Offner, Galvez Cardenas, Georg Heß, Georgii Manikhas, Govind Babu, Grigoriy Rekhtman, Guiseppe Rossi, Herlander Marques, Horia Bumbea, Huaqing Wang, Huiqiang Huang, Ilseung Choi, Irina Bulavina, Irina Lysenko, Irit Avivi, Iryna Kryachok, Jan Maciej Zaucha, Jan Novak, Joaquín Díaz, Judit Demeter, Julia Alexeeva, Jun Zhu, Kateryna Vilchevskaya, Kenichi Ishizawa, Kenny Mauricio, Kensei Tobinai, Kiyoshi Ando, Kudrat Abdulkadryrov, Lee Yung Shih, Lyudmila Kuzina, Mahmut Gumus, Maike De Wit, Marcelo Capra, Margarida Marques, Marina Golubeva, Mario Ojeda-Uribe, Maryna Kyselyova, Masafumi Taniwaki, Massimo Federico, Michael Crump, Michele Baccarani, Michinori Ogura, Miklós Egyed, Miklos Udvardy, Mitsutoshi Kurosawa, Naokuni Uike, Nuriet Khuageva Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study. The Lancet Oncology. Vol.19, No.11 (2018), 1449-1458. doi:10.1016/S1470-2045(18)30685-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/46233

Research Projects

Organizational Units

Authors

Journal Issue

Thesis

Title

Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study

Author(s)

Tadeusz Robak
 Jie Jin
 Halyna Pylypenko
 Gregor Verhoef
 Noppadol Siritanaratkul
 Johannes Drach
 Markus Raderer
 Jiri Mayer
 Juliana Pereira
 Gayane Tumyan
 Rumiko Okamoto
 Susumu Nakahara
 Peter Hu
 Carlos Appiani
 Sepideh Nemat
 Franco Cavalli
 Achiel Van Hoof
 Adriana Sheliga
 Adriana Teixeira
 Akihiro Tomita
 Albert Oriol Rocafiguera
 Alexander Suvorov
 Alexy Kuzmin
 Ali Khojasteh
 Amel Mezlini
 Anatoly Golenkov
 Andre Bosly
 Andrew Belch
 Ann Van De Velde
 Árpád Illes
 Ashis Mukhopadhyay
 Balkis Meddeb
 Bernard De Prijck
 Bernardo Garichochea
 Bulent Undar
 Caballero Gabarrón
 Carmen Cao
 Carmino Souza
 Charles Farber
 Cheol Won Suh
 Cristina Ileana Burcoveanu
 Cristina Ligia Cebotaru
 Cristina Ligia Truica
 Dai Maruyama
 David Belada
 Dina Ben Yehuda
 Dmitry Udovitsa
 Dolores
 Enrica Morra
 Ernst Späth-Schwalbe
 Eva Gonzalez-Barca
 Evgenii Osmanov
 Francisco Javier Capote
 Fritz Offner
 Galvez Cardenas
 Georg Heß
 Georgii Manikhas
 Govind Babu
 Grigoriy Rekhtman
 Guiseppe Rossi
 Herlander Marques
 Horia Bumbea
 Huaqing Wang
 Huiqiang Huang
 Ilseung Choi
 Irina Bulavina
 Irina Lysenko
 Irit Avivi
 Iryna Kryachok
 Jan Maciej Zaucha
 Jan Novak
 Joaquín Díaz
 Judit Demeter
 Julia Alexeeva
 Jun Zhu
 Kateryna Vilchevskaya
 Kenichi Ishizawa
 Kenny Mauricio
 Kensei Tobinai
 Kiyoshi Ando
 Kudrat Abdulkadryrov
 Lee Yung Shih
 Lyudmila Kuzina
 Mahmut Gumus
 Maike De Wit
 Marcelo Capra
 Margarida Marques
 Marina Golubeva
 Mario Ojeda-Uribe
 Maryna Kyselyova
 Masafumi Taniwaki
 Massimo Federico
 Michael Crump
 Michele Baccarani
 Michinori Ogura
 Miklós Egyed
 Miklos Udvardy
 Mitsutoshi Kurosawa
 Naokuni Uike
 Nuriet Khuageva

Other Contributor(s)

The First Affiliated Hospital, Zhejiang University School of Medicine
 Cherkassy Regional Oncology Center
 Janssen Research & Development
 N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
 KU Leuven– University Hospital Leuven
 Masaryk University
 Janssen
 Allgemeines KrankenHaus Wien
 Ospedale San Giovanni
 Medizinische Universitat Wien
 Faculty of Medicine, Siriraj Hospital, Mahidol University
 Universidade de Sao Paulo - USP
 Medical University of Lodz
 Janssen Pharmaceutical
 Chibanishi General Hospital

Abstract

© 2018 Elsevier Ltd Background: In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met. Methods: LYM-3002 was a randomised, open-label, phase 3 study done at 128 clinical centres in 28 countries in Asia, Europe, North America, and South America. Adult patients with confirmed stage II–IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation, were randomly assigned (1:1) to receive six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and bortezomib 1·3 mg/m2, plus oral prednisone 100 mg/m2) or R-CHOP (intravenous vincristine 1·4 mg/m2 [2 mg maximum], rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, and doxorubicin 50 mg/m2, plus oral prednisone 100 mg/m2). Randomisation was done according to a computer-generated randomisation schedule prepared by the sponsor; permuted blocks central randomisation was used (block size of 4), and was stratified by International Prognostic Index score and disease stage at diagnosis. The primary endpoint of this final analysis was overall survival, which was analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00722137, and is closed to new participants with follow-up completed. Findings: Between May 22, 2008, and Dec 5, 2011, 487 patients were enrolled and randomly assigned. 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) were included in the follow-up analysis, which included patients with data available after the primary analysis clinical cutoff date of Dec 2, 2013. After median follow-up of 82·0 months (IQR 74·1–94·2), median overall survival was significantly longer in the VR-CAP group than in the R-CHOP group (90·7 months [95% CI 71·4 to not estimable] vs 55·7 months [47·2 to 68·9]; hazard ratio 0·66 [95% CI 0·51–0·85]; p=0·001). Three new adverse events were reported since the primary analysis cutoff (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group). 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group died; the most common cause of death was progressive disease. Interpretations: Compared with R-CHOP, VR-CAP was associated with significantly longer survival, and had a manageable and expected safety profile. Our results support further assessment of VR-CAP in patients with previously untreated mantle cell lymphoma. Funding: Janssen Research & Development.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/46233

Collections

Scopus 2018