Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma
A Keith Stewart, S Vincent Rajkumar, Meletios A Dimopoulos, Tamás Masszi, Ivan Špička, Albert Oriol, Roman Hájek, Laura Rosiñol, David S Siegel, Georgi G Mihaylov, Vesselina Goranova-Marinova, Péter Rajnics, Aleksandr Suvorov, Ruben Niesvizky, Andrzej J Jakubowiak, Jesus F San-Miguel, Heinz Ludwig, Michael Wang, Vladimír Maisnar, Jiri Minarik, William I Bensinger, Maria-Victoria Mateos, Dina Ben-Yehuda, Vishal Kukreti, Naseem Zojwalla, Margaret E Tonda, Xinqun Yang, Biao Xing, Philippe Moreau, Antonio Palumbo, ASPIRE Investigators, Hermine Agis, Heinz Ludwig, Hedwig Kasparu, Michel Delforge, Hilde Demuynck, Nathalie Meuleman, Pascal Pierre, Henri Schots, Jan Van Droogenbroeck, Marie-Christiane Vekemans, Ka Lung Wu, Stefcho Goranov, Liana Gercheva, Nikolay Tzvetkov, Julian Raynov, Janet Grudeva, Georgi Mihaylov, Nizar Bahlis, Andrew Belch, Chaim Shustik, Sarit Assouline, Matthew Cheung, Kevin Song, Kuljit Grewal, Vi Dao, Vishal Kukreti, Vladimir Maisnar, Ivan Spicka, Roman Hajek, Vlastimil Scudla, Evzen Gregora, François Boue, Jean-Claude Eisenmann, Thierry Facon, Cyrille Hulin, Philippe Moreau, Eric Voog, Michel Attal, Laurent Garderet, Patrick Brück, Ralph Naumann, Stefan Knop, Hartmut Goldschmidt, Frank Griesinger, Martin Kropff, Helmut Ostermann, Eckhart Weidmann, Roland Fenk, Michael Pfreundschuh, Georgia Schilling, Athanasios Dimopoulos, Argirios Symeonidis, Janos Jakucs, Miklos Egyed, Tamas Masszi, Zoltan Gasztonyi, Agnes Nagy, Zita Borbenyi, Arpad Illes, Miklos Udvardy, Dina Ben-Yehuda, Andrei Braester, Riva Fineman, Itai Levi, Arnon Nagler, Hila Magen-Nativ, Lev Shvidel, Antonio Palumbo, Anna Cafro, Paolo De Fabritiis, Gianluca Gaidano, Mario Petrini, Pieter Sonneveld, Sonja Zweegman, Tadeusz Robak, Andrzej Hellmann, Paweł Wiszniewski, Sławomir Górnik, Jan Walewski, Mieczyslaw Komarnicki, Malgorzata Calbecka, Slawomira Kyrcz-Krzemien, Andrzej Moskwa, Alina Urbanowicz, Anca Lupu, Horia Bumbea, Andreea Moicean, Catalin Danaila, Galafteon Oltean, Kudrat Abdulkadyrov, Boris Afanasyev, Yulia Alexeeva, Dzhelil Osmanov, Galina Salogub, Nuriet Khuazheva, Larisa Mendeleeva, Alexander Suvorov, Irina Sokolova, Dragomir Marisavljevic, Aleksandar Savic, Jelena Bila, Lana Macukanovic-Golubovic, Ljiljana Tukic, Maria Echeveste Gutierrez, Jose Maria Grasa Ullrich, Albert Oriol, Felipe Prósper, Maria Victoria Mateos, Javier De la Rubia, Laura Rosiñol, Cecilie Blimark, Hareth Nahi, Simon Bolam, Faith Davies, Heather Oakervee, Mary Drake, Ashutosh Wechalekar, Cathy Williams, Fenella Willis, Supratik Basu, Keith Stewart, Moshe Talpaz, David Siegel, Luhua Wang, Francis Buadi, William Bensinger, Ruben Niesvizky, Peter Lee, Parameswaran Venugopal, Guangzhi Qu, Jeffrey Matous, Stewart Sharp, Parameswaran Hari, Sundar Jagannath, Ian Anderson, George Carrum, Vaishali Sanchorawala, Veena Charu, Gustavo Fonseca, Cristina Gasparetto, Kelly Pendergrass, Jitendra Gandhi, Delva Deauna-Limayo, Kanwaldeep Kaur Rasila, Steven Coutre, Todd Zimmerman, Kathleen Halka, Larry Anderson, Madhu Midathada, Edward Agura, Rafat Abonour, Kenneth Meehan, Amitabha Mazumder, Peter Rosen, A Keith Stewart, S Vincent Rajkumar, Meletios A Dimopoulos, Tamás Masszi, Ivan Špička, Albert Oriol, Roman Hájek, Laura Rosiñol, David S Siegel, Georgi G Mihaylov, Vesselina Goranova-Marinova, Péter Rajnics, Aleksandr Suvorov, Ruben Niesvizky, Andrzej J Jakubowiak, Jesus F San-Miguel, Heinz Ludwig, Michael Wang, Vladimír Maisnar, Jiri Minarik, William I Bensinger, Maria-Victoria Mateos, Dina Ben-Yehuda, Vishal Kukreti, Naseem Zojwalla, Margaret E Tonda, Xinqun Yang, Biao Xing, Philippe Moreau, Antonio Palumbo, ASPIRE Investigators, Hermine Agis, Heinz Ludwig, Hedwig Kasparu, Michel Delforge, Hilde Demuynck, Nathalie Meuleman, Pascal Pierre, Henri Schots, Jan Van Droogenbroeck, Marie-Christiane Vekemans, Ka Lung Wu, Stefcho Goranov, Liana Gercheva, Nikolay Tzvetkov, Julian Raynov, Janet Grudeva, Georgi Mihaylov, Nizar Bahlis, Andrew Belch, Chaim Shustik, Sarit Assouline, Matthew Cheung, Kevin Song, Kuljit Grewal, Vi Dao, Vishal Kukreti, Vladimir Maisnar, Ivan Spicka, Roman Hajek, Vlastimil Scudla, Evzen Gregora, François Boue, Jean-Claude Eisenmann, Thierry Facon, Cyrille Hulin, Philippe Moreau, Eric Voog, Michel Attal, Laurent Garderet, Patrick Brück, Ralph Naumann, Stefan Knop, Hartmut Goldschmidt, Frank Griesinger, Martin Kropff, Helmut Ostermann, Eckhart Weidmann, Roland Fenk, Michael Pfreundschuh, Georgia Schilling, Athanasios Dimopoulos, Argirios Symeonidis, Janos Jakucs, Miklos Egyed, Tamas Masszi, Zoltan Gasztonyi, Agnes Nagy, Zita Borbenyi, Arpad Illes, Miklos Udvardy, Dina Ben-Yehuda, Andrei Braester, Riva Fineman, Itai Levi, Arnon Nagler, Hila Magen-Nativ, Lev Shvidel, Antonio Palumbo, Anna Cafro, Paolo De Fabritiis, Gianluca Gaidano, Mario Petrini, Pieter Sonneveld, Sonja Zweegman, Tadeusz Robak, Andrzej Hellmann, Paweł Wiszniewski, Sławomir Górnik, Jan Walewski, Mieczyslaw Komarnicki, Malgorzata Calbecka, Slawomira Kyrcz-Krzemien, Andrzej Moskwa, Alina Urbanowicz, Anca Lupu, Horia Bumbea, Andreea Moicean, Catalin Danaila, Galafteon Oltean, Kudrat Abdulkadyrov, Boris Afanasyev, Yulia Alexeeva, Dzhelil Osmanov, Galina Salogub, Nuriet Khuazheva, Larisa Mendeleeva, Alexander Suvorov, Irina Sokolova, Dragomir Marisavljevic, Aleksandar Savic, Jelena Bila, Lana Macukanovic-Golubovic, Ljiljana Tukic, Maria Echeveste Gutierrez, Jose Maria Grasa Ullrich, Albert Oriol, Felipe Prósper, Maria Victoria Mateos, Javier De la Rubia, Laura Rosiñol, Cecilie Blimark, Hareth Nahi, Simon Bolam, Faith Davies, Heather Oakervee, Mary Drake, Ashutosh Wechalekar, Cathy Williams, Fenella Willis, Supratik Basu, Keith Stewart, Moshe Talpaz, David Siegel, Luhua Wang, Francis Buadi, William Bensinger, Ruben Niesvizky, Peter Lee, Parameswaran Venugopal, Guangzhi Qu, Jeffrey Matous, Stewart Sharp, Parameswaran Hari, Sundar Jagannath, Ian Anderson, George Carrum, Vaishali Sanchorawala, Veena Charu, Gustavo Fonseca, Cristina Gasparetto, Kelly Pendergrass, Jitendra Gandhi, Delva Deauna-Limayo, Kanwaldeep Kaur Rasila, Steven Coutre, Todd Zimmerman, Kathleen Halka, Larry Anderson, Madhu Midathada, Edward Agura, Rafat Abonour, Kenneth Meehan, Amitabha Mazumder, Peter Rosen
Abstract
Background: Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma.
Methods: We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival.
Results: Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life.
Conclusions: In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).
Source: PubMed