Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma
Meletios A Dimopoulos, Albert Oriol, Hareth Nahi, Jesus San-Miguel, Nizar J Bahlis, Saad Z Usmani, Neil Rabin, Robert Z Orlowski, Mieczyslaw Komarnicki, Kenshi Suzuki, Torben Plesner, Sung-Soo Yoon, Dina Ben Yehuda, Paul G Richardson, Hartmut Goldschmidt, Donna Reece, Steen Lisby, Nushmia Z Khokhar, Lisa O'Rourke, Christopher Chiu, Xiang Qin, Mary Guckert, Tahamtan Ahmadi, Philippe Moreau, POLLUX Investigators, Tara Cochrane, Joy Ho, James Morton, Miles Prince, Bernard De Prijck, Michel Delforge, Nathalie Meuleman, Fritz Offner, Ann Van de Velde, Koen Van Eygen, Ka Lung Wu, Nizar Bahlis, Andrew Belch, Tom Kouroukis, Marc Lalancette, Richard Leblanc, Leonard Minuk, Donna Reece, Jesse Shustik, Heather Sutherland, Darrell White, Igor-Wolfgang Blau, Wolfram Brugger, Heinz Duerk, Hartmut Goldschmidt, Georg Jacobs, Viktor Janzen, Hans Salwender, Christof Scheid, Jorg Thomalla, Niels Abildgaard, Torben Plesner, Morten Salomo, Joan Bladé, Jose Angel Hernandez Rivas, Miguel Hernandez, Maria Victoria Mateos, Alvert Oriol Rocafiguera, Jesus San-Miguel, Jaccard Arnaud, Bertrand Arnulf, Michel Attal, Lotfi Benboubker, Driss Chaoui, Olivier Decaux, Thierry Facon, Cyrille Hulin, Lionel Karlin, Margaret Macro, Philippe Moreau, Supratik Basu, Jamie Cavenagh, Gordon Cook, Mark Cook, Matthew Jenner, Martin Kaiser, Neil Rabin, Karthik Ramasamy, Matthew Streetly, Meletios-Athanasios Dimopoulos, Irit Avivi, Dina Ben Yehuda, Noam Benyamini, Shlomo Bulvik, Merav Leiba, Hila Magen, Celia Suriu, Nobuyuki Aotsuka, Tomoaki Fujisaki, Shinsuke Iida, Kazunori Imada, Takayuki Ishikawa, Hiroshi Kosugi, Morio Matsumoto, Kuniaki Meguro, Hirokazu Nagai, Shinichiro Okamoto, Atsushi Shinagawa, Kazutaka Sunami, Kenshi Suzuki, Hiroyuki Takamatu, Naoki Takezako, Hyeon Seok Eom, Jin Seok Kim, Kihyun Kim, Jaehoon Lee, Chang-ki Min, Dok Hyun Yoon, Sung-Soo Yoon, Niels Van de Donk, Sebastian Frosicki, Andrzej Hellmann, Jadwiga Holojda, Wojciech Homenda, Mieczyslaw Komarnicki, Wojciech Legiec, Tomasz Wrobel, Nuriet Khuazheva, Alexander Loginov, Nadezhda Medvedeva, Aleksandr Myasnikov, Alexander Pristupa, Andrey Proydakov, Viktor Rossiev, Irina Samarina, Olga Samoilova, Sergey Voloshin, Per Axelsson, Cecilie Blimark, Kristina Carlson, Max Flogegard, Markus Hansson, Nahi Hareth, Olga Stromberg, Cheng-Shyong Chang, Tsai-Yun Chen, Shang-Yi Huang, Tung-Liang Lin, Su-Peng Yeh, Larry Anderson, Ajai Chari, Andrzej Jakubowiak, Jonathan Kaufman, Shaji Kumar, Jacob Laubach, Alka Mallik, Amitabha Mazumder, Mohit Narang, Robert Orlowski, Shachar Peles, Stefano Tarantolo, Guidot Tricot, Saad Usmani, Christopher Yasenchak, Meletios A Dimopoulos, Albert Oriol, Hareth Nahi, Jesus San-Miguel, Nizar J Bahlis, Saad Z Usmani, Neil Rabin, Robert Z Orlowski, Mieczyslaw Komarnicki, Kenshi Suzuki, Torben Plesner, Sung-Soo Yoon, Dina Ben Yehuda, Paul G Richardson, Hartmut Goldschmidt, Donna Reece, Steen Lisby, Nushmia Z Khokhar, Lisa O'Rourke, Christopher Chiu, Xiang Qin, Mary Guckert, Tahamtan Ahmadi, Philippe Moreau, POLLUX Investigators, Tara Cochrane, Joy Ho, James Morton, Miles Prince, Bernard De Prijck, Michel Delforge, Nathalie Meuleman, Fritz Offner, Ann Van de Velde, Koen Van Eygen, Ka Lung Wu, Nizar Bahlis, Andrew Belch, Tom Kouroukis, Marc Lalancette, Richard Leblanc, Leonard Minuk, Donna Reece, Jesse Shustik, Heather Sutherland, Darrell White, Igor-Wolfgang Blau, Wolfram Brugger, Heinz Duerk, Hartmut Goldschmidt, Georg Jacobs, Viktor Janzen, Hans Salwender, Christof Scheid, Jorg Thomalla, Niels Abildgaard, Torben Plesner, Morten Salomo, Joan Bladé, Jose Angel Hernandez Rivas, Miguel Hernandez, Maria Victoria Mateos, Alvert Oriol Rocafiguera, Jesus San-Miguel, Jaccard Arnaud, Bertrand Arnulf, Michel Attal, Lotfi Benboubker, Driss Chaoui, Olivier Decaux, Thierry Facon, Cyrille Hulin, Lionel Karlin, Margaret Macro, Philippe Moreau, Supratik Basu, Jamie Cavenagh, Gordon Cook, Mark Cook, Matthew Jenner, Martin Kaiser, Neil Rabin, Karthik Ramasamy, Matthew Streetly, Meletios-Athanasios Dimopoulos, Irit Avivi, Dina Ben Yehuda, Noam Benyamini, Shlomo Bulvik, Merav Leiba, Hila Magen, Celia Suriu, Nobuyuki Aotsuka, Tomoaki Fujisaki, Shinsuke Iida, Kazunori Imada, Takayuki Ishikawa, Hiroshi Kosugi, Morio Matsumoto, Kuniaki Meguro, Hirokazu Nagai, Shinichiro Okamoto, Atsushi Shinagawa, Kazutaka Sunami, Kenshi Suzuki, Hiroyuki Takamatu, Naoki Takezako, Hyeon Seok Eom, Jin Seok Kim, Kihyun Kim, Jaehoon Lee, Chang-ki Min, Dok Hyun Yoon, Sung-Soo Yoon, Niels Van de Donk, Sebastian Frosicki, Andrzej Hellmann, Jadwiga Holojda, Wojciech Homenda, Mieczyslaw Komarnicki, Wojciech Legiec, Tomasz Wrobel, Nuriet Khuazheva, Alexander Loginov, Nadezhda Medvedeva, Aleksandr Myasnikov, Alexander Pristupa, Andrey Proydakov, Viktor Rossiev, Irina Samarina, Olga Samoilova, Sergey Voloshin, Per Axelsson, Cecilie Blimark, Kristina Carlson, Max Flogegard, Markus Hansson, Nahi Hareth, Olga Stromberg, Cheng-Shyong Chang, Tsai-Yun Chen, Shang-Yi Huang, Tung-Liang Lin, Su-Peng Yeh, Larry Anderson, Ajai Chari, Andrzej Jakubowiak, Jonathan Kaufman, Shaji Kumar, Jacob Laubach, Alka Mallik, Amitabha Mazumder, Mohit Narang, Robert Orlowski, Shachar Peles, Stefano Tarantolo, Guidot Tricot, Saad Usmani, Christopher Yasenchak
Abstract
Background: Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma.
Methods: In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival.
Results: At a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval [CI], 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan-Meier rate of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in the control group. A significantly higher rate of overall response was observed in the daratumumab group than in the control group (92.9% vs. 76.4%, P<0.001), as was a higher rate of complete response or better (43.1% vs. 19.2%, P<0.001). In the daratumumab group, 22.4% of the patients had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells), as compared with 4.6% of those in the control group (P<0.001); results below the threshold for minimal residual disease were associated with improved outcomes. The most common adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the patients in the daratumumab group vs. 37.0% of those in the control group), thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%). Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2.
Conclusions: The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma. Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy. (Funded by Janssen Research and Development; POLLUX ClinicalTrials.gov number, NCT02076009 .).
Source: PubMed