Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma
María-Victoria Mateos, Meletios A Dimopoulos, Michele Cavo, Kenshi Suzuki, Andrzej Jakubowiak, Stefan Knop, Chantal Doyen, Paulo Lucio, Zsolt Nagy, Polina Kaplan, Ludek Pour, Mark Cook, Sebastian Grosicki, Andre Crepaldi, Anna M Liberati, Philip Campbell, Tatiana Shelekhova, Sung-Soo Yoon, Genadi Iosava, Tomoaki Fujisaki, Mamta Garg, Christopher Chiu, Jianping Wang, Robin Carson, Wendy Crist, William Deraedt, Huong Nguyen, Ming Qi, Jesus San-Miguel, ALCYONE Trial Investigators, Dorotea Fantl, Daniel Bar, Dardo Alberto Riveros, Gustavo Jarchum, Alicia Ines Enrico, Astrid Pavlovsky, Wilfrid Jaksic, Jeffrey Szer, Nick Murphy, Sonali Sadawarte, Cecily Forsyth, Robert Blum, Joy Ho, Anthony Mills, Noemi Horvath, Greet Bries, Koenraad Van Eygen, Ka Lung Wu, Dries Deeren, Steven Van Steenweghen, Zwi Nisan Berneman, Fritz Offner, Philippe Mineur, Rik Schots, Vania Hungria, James Maciel, Angelo Maiolino, Walter Braga, Suzanna Barbosa, Jacques Kaufman, Wolney Barreto, Luciana Oliveira, Laura Fogliatto, Nelson Castro, Danielle Farias, Rodrigo Santucci, Nelson Hamerschlak, Fernando Duarte, Evgueniy Hadjiev, Atanas Radinoff, Nikolay Tzvetkov, Liana Gercheva-Kyuchukova, Georgi Mihaylov, Gancho Yotov, Julian Raynov, Liliya Sivcheva, Stefcho Goranov, Slobodanka O Kolonic, Zeljka Skunca, Josip Batinic, Vlatko Pejsa, Ivan Spicka, Evzen Gregora, Vastimil Scudla, Vladimir Maisnar, Roman Hajek, Alexandra Jungova, Mamia Zodelava, Ekaterine Gaprindashvili, Stephan Fuhrmann, Jan Schleicher, Christian Jakob, Joy Priscilla Dickinson, Heidrun Hindahl, Georg Jacobs, Aristeidis Chaidos, Charles Crawley, Faris Al-Rafaie, Satyajit Sahu, Michael Hamblin, Sudhakaran Makkuni, Antonina Zhelyazkova, Argiris Symeonidis, A Anagnostopoulos, Vasiliki Pappa, Konstantinos Anargyrou, Panagiotis Zikos, Arpad Illes, Arpad Szomor, Tamas Masszi, Gabor Mikala, Andras Rosta, Miklos Egyed, Gergely Varga, Alessandro Rambaldi, Mario Boccadoro, Antonio Palumbo, Massimo Offidani, Roberto Foa, Giuseppe Rossi, Anna Maria Cafro, Pellegrino Musto, Francesco Fabbiano, Alessandro Corso, Francesco di Raimondo, Renato Zambello, Marco Gobbi, Koji Nagafuji, Shinksuke Iida, Morio Matsumoto, Naoki Takezako, Kazutaka Sunami, Hiroshi Kosugi, Takayuki Ishikawa, Koji Izutsu, Kazunori Imada, Hitomi Kaneko, Isamu Sugiura, Atsushi Shinagawa, Yasushi Onishi, Hiroyuki Takamatsu, Toshiki Uchida, Kousei Matsue, Atsushi Wake, Nobuyuki Aotsuka, Won Sik Lee, Hyeon Seok Eom, Ki Hyun Kim, Sunghyun Kim, Dok Hyun Yoon, Jeeong-Ok Lee, Jin Seok Kim, Jae Hoon Lee, Chang-ki Min, Jejung Lee, Svetlana Stankovic, Borche Georgievski, Lidija Chevreska, Jaroslaw Czyz, Janusz Kloczko, Wieslaw Wiktor Jedrzejczak, Wojciech Homenda, Dariusz Woszczyk, Jadwiga Holojda, Marek Hus, Andrzej Hellmann, Tomasz Wrobel, Jan Walewski, Joana Martins, Graca Esteves, Angelo Martins, Emanuil Gheorghita, Gabriela Borsaru, Viola Maria Popov, Catalin Doru Danaila, Mihaela Lazaroiu, Sergey Alekseev, Olga Samoilova, Alexander Pristupa, Dmitry Udovitsa, Viktor Rossiev, Boris Afanasyev, Tatiana Konstantinova, Irina Samarina, Yurii Dunaev, Kamil Kaplanov, Nenad Milanovic, Goran Marjanovic, Dragomir Marisavljevic, Darjana Jovanovic, Zoran Milojevic, Aleksander Savic, Miguel Teodoro Hernandez Garcia, Javier De La Rubia, Carmen Couto Caro, Jaime Perez de Oteyza, Joan Blade, Yolanda Gonzales, Albert Oriol, Paula Rodriguez, Jesus Martin Sanchez, Maria Sole, Felipe de Arriba, Ana Sureda, Joaquin Martinez, Miguel Angel Alvarez Rivas, Mercedes Gironella, Luis Felipe Casado Montero, Cristina Encinas, Luis Palomera, Jose Luis Sastre Moral, Munci Yagci, Fevzi Altuntas, Gulsum Ozet, Guner Hayri Ozsan, Filiz Vural, Mehmet Turgut, Burhan Turgut, Burhan Ferhanoglu, Ali Zahit Bolaman, Sevgi Kalayoglu Besisik, Ali Unal, Meral Beksac, Halyna Pylypenko, Borys Samura, Tetiana Popovs’ka, Zvenyslava Masliak, Natalia Glushko, Grygoriy Rekhtman, Mehdi Moezi, Marcos de Lima, Malek Ehsan, Christopher Vaughn, Eloy Roman, Gary Schiller, Haresh Jhangiani, Olukemi Wallace, Viran Holden, Jessica Snider, Stephen Noga, David Haile, Anas Alraws, María-Victoria Mateos, Meletios A Dimopoulos, Michele Cavo, Kenshi Suzuki, Andrzej Jakubowiak, Stefan Knop, Chantal Doyen, Paulo Lucio, Zsolt Nagy, Polina Kaplan, Ludek Pour, Mark Cook, Sebastian Grosicki, Andre Crepaldi, Anna M Liberati, Philip Campbell, Tatiana Shelekhova, Sung-Soo Yoon, Genadi Iosava, Tomoaki Fujisaki, Mamta Garg, Christopher Chiu, Jianping Wang, Robin Carson, Wendy Crist, William Deraedt, Huong Nguyen, Ming Qi, Jesus San-Miguel, ALCYONE Trial Investigators, Dorotea Fantl, Daniel Bar, Dardo Alberto Riveros, Gustavo Jarchum, Alicia Ines Enrico, Astrid Pavlovsky, Wilfrid Jaksic, Jeffrey Szer, Nick Murphy, Sonali Sadawarte, Cecily Forsyth, Robert Blum, Joy Ho, Anthony Mills, Noemi Horvath, Greet Bries, Koenraad Van Eygen, Ka Lung Wu, Dries Deeren, Steven Van Steenweghen, Zwi Nisan Berneman, Fritz Offner, Philippe Mineur, Rik Schots, Vania Hungria, James Maciel, Angelo Maiolino, Walter Braga, Suzanna Barbosa, Jacques Kaufman, Wolney Barreto, Luciana Oliveira, Laura Fogliatto, Nelson Castro, Danielle Farias, Rodrigo Santucci, Nelson Hamerschlak, Fernando Duarte, Evgueniy Hadjiev, Atanas Radinoff, Nikolay Tzvetkov, Liana Gercheva-Kyuchukova, Georgi Mihaylov, Gancho Yotov, Julian Raynov, Liliya Sivcheva, Stefcho Goranov, Slobodanka O Kolonic, Zeljka Skunca, Josip Batinic, Vlatko Pejsa, Ivan Spicka, Evzen Gregora, Vastimil Scudla, Vladimir Maisnar, Roman Hajek, Alexandra Jungova, Mamia Zodelava, Ekaterine Gaprindashvili, Stephan Fuhrmann, Jan Schleicher, Christian Jakob, Joy Priscilla Dickinson, Heidrun Hindahl, Georg Jacobs, Aristeidis Chaidos, Charles Crawley, Faris Al-Rafaie, Satyajit Sahu, Michael Hamblin, Sudhakaran Makkuni, Antonina Zhelyazkova, Argiris Symeonidis, A Anagnostopoulos, Vasiliki Pappa, Konstantinos Anargyrou, Panagiotis Zikos, Arpad Illes, Arpad Szomor, Tamas Masszi, Gabor Mikala, Andras Rosta, Miklos Egyed, Gergely Varga, Alessandro Rambaldi, Mario Boccadoro, Antonio Palumbo, Massimo Offidani, Roberto Foa, Giuseppe Rossi, Anna Maria Cafro, Pellegrino Musto, Francesco Fabbiano, Alessandro Corso, Francesco di Raimondo, Renato Zambello, Marco Gobbi, Koji Nagafuji, Shinksuke Iida, Morio Matsumoto, Naoki Takezako, Kazutaka Sunami, Hiroshi Kosugi, Takayuki Ishikawa, Koji Izutsu, Kazunori Imada, Hitomi Kaneko, Isamu Sugiura, Atsushi Shinagawa, Yasushi Onishi, Hiroyuki Takamatsu, Toshiki Uchida, Kousei Matsue, Atsushi Wake, Nobuyuki Aotsuka, Won Sik Lee, Hyeon Seok Eom, Ki Hyun Kim, Sunghyun Kim, Dok Hyun Yoon, Jeeong-Ok Lee, Jin Seok Kim, Jae Hoon Lee, Chang-ki Min, Jejung Lee, Svetlana Stankovic, Borche Georgievski, Lidija Chevreska, Jaroslaw Czyz, Janusz Kloczko, Wieslaw Wiktor Jedrzejczak, Wojciech Homenda, Dariusz Woszczyk, Jadwiga Holojda, Marek Hus, Andrzej Hellmann, Tomasz Wrobel, Jan Walewski, Joana Martins, Graca Esteves, Angelo Martins, Emanuil Gheorghita, Gabriela Borsaru, Viola Maria Popov, Catalin Doru Danaila, Mihaela Lazaroiu, Sergey Alekseev, Olga Samoilova, Alexander Pristupa, Dmitry Udovitsa, Viktor Rossiev, Boris Afanasyev, Tatiana Konstantinova, Irina Samarina, Yurii Dunaev, Kamil Kaplanov, Nenad Milanovic, Goran Marjanovic, Dragomir Marisavljevic, Darjana Jovanovic, Zoran Milojevic, Aleksander Savic, Miguel Teodoro Hernandez Garcia, Javier De La Rubia, Carmen Couto Caro, Jaime Perez de Oteyza, Joan Blade, Yolanda Gonzales, Albert Oriol, Paula Rodriguez, Jesus Martin Sanchez, Maria Sole, Felipe de Arriba, Ana Sureda, Joaquin Martinez, Miguel Angel Alvarez Rivas, Mercedes Gironella, Luis Felipe Casado Montero, Cristina Encinas, Luis Palomera, Jose Luis Sastre Moral, Munci Yagci, Fevzi Altuntas, Gulsum Ozet, Guner Hayri Ozsan, Filiz Vural, Mehmet Turgut, Burhan Turgut, Burhan Ferhanoglu, Ali Zahit Bolaman, Sevgi Kalayoglu Besisik, Ali Unal, Meral Beksac, Halyna Pylypenko, Borys Samura, Tetiana Popovs’ka, Zvenyslava Masliak, Natalia Glushko, Grygoriy Rekhtman, Mehdi Moezi, Marcos de Lima, Malek Ehsan, Christopher Vaughn, Eloy Roman, Gary Schiller, Haresh Jhangiani, Olukemi Wallace, Viran Holden, Jessica Snider, Stephen Noga, David Haile, Anas Alraws
Abstract
Background: The combination of bortezomib, melphalan, and prednisone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. Daratumumab has shown efficacy in combination with standard-of-care regimens in patients with relapsed or refractory multiple myeloma.
Methods: In this phase 3 trial, we randomly assigned 706 patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation to receive nine cycles of bortezomib, melphalan, and prednisone either alone (control group) or with daratumumab (daratumumab group) until disease progression. The primary end point was progression-free survival.
Results: At a median follow-up of 16.5 months in a prespecified interim analysis, the 18-month progression-free survival rate was 71.6% (95% confidence interval [CI], 65.5 to 76.8) in the daratumumab group and 50.2% (95% CI, 43.2 to 56.7) in the control group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The overall response rate was 90.9% in the daratumumab group, as compared with 73.9% in the control group (P<0.001), and the rate of complete response or better (including stringent complete response) was 42.6%, versus 24.4% (P<0.001). In the daratumumab group, 22.3% of the patients were negative for minimal residual disease (at a threshold of 1 tumor cell per 105 white cells), as compared with 6.2% of those in the control group (P<0.001). The most common adverse events of grade 3 or 4 were hematologic: neutropenia (in 39.9% of the patients in the daratumumab group and in 38.7% of those in the control group), thrombocytopenia (in 34.4% and 37.6%, respectively), and anemia (in 15.9% and 19.8%, respectively). The rate of grade 3 or 4 infections was 23.1% in the daratumumab group and 14.7% in the control group; the rate of treatment discontinuation due to infections was 0.9% and 1.4%, respectively. Daratumumab-associated infusion-related reactions occurred in 27.7% of the patients.
Conclusions: Among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, daratumumab combined with bortezomib, melphalan, and prednisone resulted in a lower risk of disease progression or death than the same regimen without daratumumab. The daratumumab-containing regimen was associated with more grade 3 or 4 infections. (Funded by Janssen Research and Development; ALCYONE ClinicalTrials.gov number, NCT02195479 .).
Source: PubMed