Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma
Tadeusz Robak, Huiqiang Huang, Jie Jin, Jun Zhu, Ting Liu, Olga Samoilova, Halyna Pylypenko, Gregor Verhoef, Noppadol Siritanaratkul, Evgenii Osmanov, Julia Alexeeva, Juliana Pereira, Johannes Drach, Jiri Mayer, Xiaonan Hong, Rumiko Okamoto, Lixia Pei, Brendan Rooney, Helgi van de Velde, Franco Cavalli, LYM-3002 Investigators, Johannes Drach, Richard Greil, Gregor Verhoef, Andre Bosly, Fritz Offner, Ann Van De Velde, Achiel Van Hoof, Steven Van Steenweghen, Pierre Zachee, Bernard De Prijck, Juliana Pereira, Bernardo Garichochea, Vladimir Lima, Marcelo Capra, Adriana Sheliga, Carmino Souza, Patricia Santi, Andrew Belch, Michael Crump, Carmen Cao, Kenny Mauricio, Galvez Cardenas, Sergio Cancelado, Jiri Mayer, Jan Novak, David Belada, Remy Gressin, Steven Le Gouill, Mario Ojeda-Uribe, Ernst Späth-Schwalbe, Georg Heß, Maike De Wit, Judit Demeter, Miklós Egyed, Zita Borbenyi, Zoltán Gasztonyi, Árpád Illes, Miklos Udvardy, Govind Babu, Ashis Mukhopadhyay, Sreejith Nair, Ofer Shpilberg, Irit Avivi, Dina Ben Yehuda, Massimo Federico, Guiseppe Rossi, Michele Baccarani, Enrica Morra, Umberto Vitolo, Yoshiharu Maeda, Michinori Ogura, Rumiko Okamoto, Masafumi Taniwaki, Yasuhito Terui, Kensei Tobinai, Naokuni Uike, Kiyoshi Ando, Kenichi Ishizawa, Mitsutoshi Kurosawa, Akihiro Tomita, Huiqiang Huang, Jie Jin, Jun Zhu, Ting Liu, Xiaonan Hong, Xiaoyan Ke, Huaqing Wang, Zhixiang Shen, Yuankai Shi, Zhao Wang, Tadeusz Robak, Jan Maciej Zaucha, Sebastian Grosicki, Adriana Teixeira, Herlander Marques, Margarida Marques, Sung-Soo Yoon, Cheol Won Suh, Cristina Ileana Burcoveanu, Razvan Stoia, Horia Bumbea, Cristina Ligia Cebotaru, Cristina-Ligia Truica, Olga Samoilova, Julia Alexeeva, Evgenii Osmanov, Irina Lysenko, Alexander Suvorov, Oleg Gladkov, Georgii Manikhas, Tatiana Scheider, Nuriet Khuageva, Alexy Kuzmin, Kudrat Abdulkadryrov, Irina Bulavina, Yuri Dunaev, Lyudmila Kuzina, Anatoly Golenkov, Marina Golubeva, Olga Serduk, Yurii Lorie, Viacheslav Pavlov, Vladimir Merkulov, Dmitry Udovitsa, Yeow Tee Goh, Reyes Arranz, Dolores, Caballero Gabarrón, Albert Oriol Rocafiguera, Francisco Javier Capote, Joaquín Díaz, Eva Gonzalez-Barca, Lee-Yung Shih, Noppadol Siritanaratkul, Udomsak Bunworasate, Weerasak Nawarawong, Suporn Chuncharunee, Balkis Meddeb, Amel Mezlini, Bulent Undar, Mahmut Gumus, Halyna Pylypenko, Kateryna Vilchevskaya, Zvenyslava Masliak, Grigoriy Rekhtman, Polina Kaplan, Iryna Kryachok, Maryna Kyselyova, Charles Farber, Vijay Rao Phooshkooru, Ali Khojasteh, Tadeusz Robak, Huiqiang Huang, Jie Jin, Jun Zhu, Ting Liu, Olga Samoilova, Halyna Pylypenko, Gregor Verhoef, Noppadol Siritanaratkul, Evgenii Osmanov, Julia Alexeeva, Juliana Pereira, Johannes Drach, Jiri Mayer, Xiaonan Hong, Rumiko Okamoto, Lixia Pei, Brendan Rooney, Helgi van de Velde, Franco Cavalli, LYM-3002 Investigators, Johannes Drach, Richard Greil, Gregor Verhoef, Andre Bosly, Fritz Offner, Ann Van De Velde, Achiel Van Hoof, Steven Van Steenweghen, Pierre Zachee, Bernard De Prijck, Juliana Pereira, Bernardo Garichochea, Vladimir Lima, Marcelo Capra, Adriana Sheliga, Carmino Souza, Patricia Santi, Andrew Belch, Michael Crump, Carmen Cao, Kenny Mauricio, Galvez Cardenas, Sergio Cancelado, Jiri Mayer, Jan Novak, David Belada, Remy Gressin, Steven Le Gouill, Mario Ojeda-Uribe, Ernst Späth-Schwalbe, Georg Heß, Maike De Wit, Judit Demeter, Miklós Egyed, Zita Borbenyi, Zoltán Gasztonyi, Árpád Illes, Miklos Udvardy, Govind Babu, Ashis Mukhopadhyay, Sreejith Nair, Ofer Shpilberg, Irit Avivi, Dina Ben Yehuda, Massimo Federico, Guiseppe Rossi, Michele Baccarani, Enrica Morra, Umberto Vitolo, Yoshiharu Maeda, Michinori Ogura, Rumiko Okamoto, Masafumi Taniwaki, Yasuhito Terui, Kensei Tobinai, Naokuni Uike, Kiyoshi Ando, Kenichi Ishizawa, Mitsutoshi Kurosawa, Akihiro Tomita, Huiqiang Huang, Jie Jin, Jun Zhu, Ting Liu, Xiaonan Hong, Xiaoyan Ke, Huaqing Wang, Zhixiang Shen, Yuankai Shi, Zhao Wang, Tadeusz Robak, Jan Maciej Zaucha, Sebastian Grosicki, Adriana Teixeira, Herlander Marques, Margarida Marques, Sung-Soo Yoon, Cheol Won Suh, Cristina Ileana Burcoveanu, Razvan Stoia, Horia Bumbea, Cristina Ligia Cebotaru, Cristina-Ligia Truica, Olga Samoilova, Julia Alexeeva, Evgenii Osmanov, Irina Lysenko, Alexander Suvorov, Oleg Gladkov, Georgii Manikhas, Tatiana Scheider, Nuriet Khuageva, Alexy Kuzmin, Kudrat Abdulkadryrov, Irina Bulavina, Yuri Dunaev, Lyudmila Kuzina, Anatoly Golenkov, Marina Golubeva, Olga Serduk, Yurii Lorie, Viacheslav Pavlov, Vladimir Merkulov, Dmitry Udovitsa, Yeow Tee Goh, Reyes Arranz, Dolores, Caballero Gabarrón, Albert Oriol Rocafiguera, Francisco Javier Capote, Joaquín Díaz, Eva Gonzalez-Barca, Lee-Yung Shih, Noppadol Siritanaratkul, Udomsak Bunworasate, Weerasak Nawarawong, Suporn Chuncharunee, Balkis Meddeb, Amel Mezlini, Bulent Undar, Mahmut Gumus, Halyna Pylypenko, Kateryna Vilchevskaya, Zvenyslava Masliak, Grigoriy Rekhtman, Polina Kaplan, Iryna Kryachok, Maryna Kyselyova, Charles Farber, Vijay Rao Phooshkooru, Ali Khojasteh
Abstract
Background: The proteasome inhibitor bortezomib was initially approved for the treatment of relapsed mantle-cell lymphoma. We investigated whether substituting bortezomib for vincristine in frontline therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could improve outcomes in patients with newly diagnosed mantle-cell lymphoma.
Methods: In this phase 3 trial, we randomly assigned 487 adults with newly diagnosed mantle-cell lymphoma who were ineligible or not considered for stem-cell transplantation to receive six to eight 21-day cycles of R-CHOP intravenously on day 1 (with prednisone administered orally on days 1 to 5) or VR-CAP (R-CHOP regimen, but replacing vincristine with bortezomib at a dose of 1.3 mg per square meter of body-surface area on days 1, 4, 8, and 11). The primary end point was progression-free survival.
Results: After a median follow-up of 40 months, median progression-free survival (according to independent radiologic review) was 14.4 months in the R-CHOP group versus 24.7 months in the VR-CAP group (hazard ratio favoring the VR-CAP group, 0.63; P<0.001), a relative improvement of 59%. On the basis of investigator assessment, the median durations of progression-free survival were 16.1 months and 30.7 months, respectively (hazard ratio, 0.51; P<0.001), a relative improvement of 96%. Secondary end points were consistently improved in the VR-CAP group, including the complete response rate (42% vs. 53%), the median duration of complete response (18.0 months vs. 42.1 months), the median treatment-free interval (20.5 months vs. 40.6 months), and the 4-year overall survival rate (54% vs. 64%). Rates of neutropenia and thrombocytopenia were higher in the VR-CAP group.
Conclusions: VR-CAP was more effective than R-CHOP in patients with newly diagnosed mantle-cell lymphoma but at the cost of increased hematologic toxicity. (Funded by Janssen Research and Development and Millennium Pharmaceuticals; LYM-3002 ClinicalTrials.gov number, NCT00722137.).
Source: PubMed