Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma
Antonio Palumbo, Asher Chanan-Khan, Katja Weisel, Ajay K Nooka, Tamas Masszi, Meral Beksac, Ivan Spicka, Vania Hungria, Markus Munder, Maria V Mateos, Tomer M Mark, Ming Qi, Jordan Schecter, Himal Amin, Xiang Qin, William Deraedt, Tahamtan Ahmadi, Andrew Spencer, Pieter Sonneveld, CASTOR Investigators, Andrew Spencer, Jane Estell, Hang Quach, Noemi Horvath, Nick Murphy, Bradley Augustson, Cindy Lee, Maura Romeo, Vladmir de Lima, Nelson Castro, Nelson Hamerschlak, Vania Hungria, Wolney Barreto, Carlos Eduardo Miguel, Marcelo Capra, Ludek Pour, Vladimír Maisnar, Roman Hajek, Ivan Spicka, Evžen Gregora, Monika Engelhardt, Roland Repp, Martina Teichmann, Roland Fenk, Markus Munder, Christian Langer, Wolfram Jung, Mascha Binder, Florian Bassermann, Katja Weisel, Matthias Vohringer, Stefan Knop, Martin Schmidt-Hieber, Elvira Altai, Zsolt Nagy, Arpad Szomor, Zoltan Gasztonyi, Arpad Illes, Tamas Masszi, Angelo Michele Carella, Antonio Palumbo, Roberto Foa, Pellegrino Musto, Michele Cavo, Paolo Corradini, Francesco Di Raimondo, Alberto Bosi, Alessandro Corso, Felicetto Ferrara, Nicola Cascavilla, Alessandro Rambaldi, ChangKi Min, Ho-Jin Shin, ByungSoo Kim, Jejung Lee, JoonSeong Park, Yeung Chul Mun, Dok Hyun Yoon, Jae-Cheol Jo, Roberto Ovilla, David Gomez, Liane Te Boome, Alexandra Johanna Croockewit, Gerard Bos, P A Von Dem Borne, E Vellenga, Saskia Klein, Mark-David Levin, M Westerman, Sebastian Grosicki, Mieczyslaw Komarnicki, Slawomira Kyrcz-Krzemien, Artur Jurczyszyn, Jan Walewski, Krzysztof Warzocha, Olga Samoilova, Nuriet Khuazheva, Alexander Pristupa, Viktor Rossiev, Vladimir Melnichenko, Tatiana Chagorova, Olga Serduk, Dmitry Udovitsa, Vladimir Vladimirov, Andrey Proydakov, Javier De la Rubia, Isidro Jarque, Maria Victoria Mateos, Joaquin Martinez, Eugenio Gimenez, Felipe Casado, Maria Jesus Blanchard, Jose Angel Hernandez Rivas, Birgitta Lauri, Karin Forsberg, Bertil Uggla, Kristina Carlsson, Markus Hansson, Lucia Ahlberg, Maria Strandberg, Peter Kragsbjerg, Ali Unal, Meral Beksac, Emin Kaya, Abdullah Hacihanefioglu, Seckin Cagirgan, Tulin Tuglular, Sevgi Besisik, Halyna Pylypenko, Borys Samura, Nataliia Glushko, Polina Kaplan, Zvenyslava Masliak, Evgeniy Karamanesht, Sibirina Korenkova, Igor Skrypnyk, Hanna Oliynyk, Iryna Dyagil, Michael Bar, Suzanne Lentzsch, Mouhammed Jameel Kyasa, Brea Lipe, Diego de Idiaquez, Asher Chanan Khan, Leonard Klein, William Bensinger, Damian J Green, Brendan Weiss, Ajay Nooka, Kent H Holland, Tomer Mark, Peter M Voorhees, Eric Winer, Gordan Srkalovic, Robert Vescio, Eva Medvedova, Thomas Cosgriff, Jacob Laubach, Antonio Palumbo, Asher Chanan-Khan, Katja Weisel, Ajay K Nooka, Tamas Masszi, Meral Beksac, Ivan Spicka, Vania Hungria, Markus Munder, Maria V Mateos, Tomer M Mark, Ming Qi, Jordan Schecter, Himal Amin, Xiang Qin, William Deraedt, Tahamtan Ahmadi, Andrew Spencer, Pieter Sonneveld, CASTOR Investigators, Andrew Spencer, Jane Estell, Hang Quach, Noemi Horvath, Nick Murphy, Bradley Augustson, Cindy Lee, Maura Romeo, Vladmir de Lima, Nelson Castro, Nelson Hamerschlak, Vania Hungria, Wolney Barreto, Carlos Eduardo Miguel, Marcelo Capra, Ludek Pour, Vladimír Maisnar, Roman Hajek, Ivan Spicka, Evžen Gregora, Monika Engelhardt, Roland Repp, Martina Teichmann, Roland Fenk, Markus Munder, Christian Langer, Wolfram Jung, Mascha Binder, Florian Bassermann, Katja Weisel, Matthias Vohringer, Stefan Knop, Martin Schmidt-Hieber, Elvira Altai, Zsolt Nagy, Arpad Szomor, Zoltan Gasztonyi, Arpad Illes, Tamas Masszi, Angelo Michele Carella, Antonio Palumbo, Roberto Foa, Pellegrino Musto, Michele Cavo, Paolo Corradini, Francesco Di Raimondo, Alberto Bosi, Alessandro Corso, Felicetto Ferrara, Nicola Cascavilla, Alessandro Rambaldi, ChangKi Min, Ho-Jin Shin, ByungSoo Kim, Jejung Lee, JoonSeong Park, Yeung Chul Mun, Dok Hyun Yoon, Jae-Cheol Jo, Roberto Ovilla, David Gomez, Liane Te Boome, Alexandra Johanna Croockewit, Gerard Bos, P A Von Dem Borne, E Vellenga, Saskia Klein, Mark-David Levin, M Westerman, Sebastian Grosicki, Mieczyslaw Komarnicki, Slawomira Kyrcz-Krzemien, Artur Jurczyszyn, Jan Walewski, Krzysztof Warzocha, Olga Samoilova, Nuriet Khuazheva, Alexander Pristupa, Viktor Rossiev, Vladimir Melnichenko, Tatiana Chagorova, Olga Serduk, Dmitry Udovitsa, Vladimir Vladimirov, Andrey Proydakov, Javier De la Rubia, Isidro Jarque, Maria Victoria Mateos, Joaquin Martinez, Eugenio Gimenez, Felipe Casado, Maria Jesus Blanchard, Jose Angel Hernandez Rivas, Birgitta Lauri, Karin Forsberg, Bertil Uggla, Kristina Carlsson, Markus Hansson, Lucia Ahlberg, Maria Strandberg, Peter Kragsbjerg, Ali Unal, Meral Beksac, Emin Kaya, Abdullah Hacihanefioglu, Seckin Cagirgan, Tulin Tuglular, Sevgi Besisik, Halyna Pylypenko, Borys Samura, Nataliia Glushko, Polina Kaplan, Zvenyslava Masliak, Evgeniy Karamanesht, Sibirina Korenkova, Igor Skrypnyk, Hanna Oliynyk, Iryna Dyagil, Michael Bar, Suzanne Lentzsch, Mouhammed Jameel Kyasa, Brea Lipe, Diego de Idiaquez, Asher Chanan Khan, Leonard Klein, William Bensinger, Damian J Green, Brendan Weiss, Ajay Nooka, Kent H Holland, Tomer Mark, Peter M Voorhees, Eric Winer, Gordan Srkalovic, Robert Vescio, Eva Medvedova, Thomas Cosgriff, Jacob Laubach
Abstract
Background: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma.
Methods: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival.
Results: A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group. After a median follow-up period of 7.4 months, the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95% confidence interval, 0.28 to 0.53; P<0.001). The rate of overall response was higher in the daratumumab group than in the control group (82.9% vs. 63.2%, P<0.001), as were the rates of very good partial response or better (59.2% vs. 29.1%, P<0.001) and complete response or better (19.2% vs. 9.0%, P=0.001). Three of the most common grade 3 or 4 adverse events reported in the daratumumab group and the control group were thrombocytopenia (45.3% and 32.9%, respectively), anemia (14.4% and 16.0%, respectively), and neutropenia (12.8% and 4.2%, respectively). Infusion-related reactions that were associated with daratumumab treatment were reported in 45.3% of the patients in the daratumumab group; these reactions were mostly grade 1 or 2 (grade 3 in 8.6% of the patients), and in 98.2% of these patients, they occurred during the first infusion.
Conclusions: Among patients with relapsed or relapsed and refractory multiple myeloma, daratumumab in combination with bortezomib and dexamethasone resulted in significantly longer progression-free survival than bortezomib and dexamethasone alone and was associated with infusion-related reactions and higher rates of thrombocytopenia and neutropenia than bortezomib and dexamethasone alone. (Funded by Janssen Research and Development; ClinicalTrials.gov number, NCT02136134.).
Source: PubMed