Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma
Thierry Facon, Shaji Kumar, Torben Plesner, Robert Z Orlowski, Philippe Moreau, Nizar Bahlis, Supratik Basu, Hareth Nahi, Cyrille Hulin, Hang Quach, Hartmut Goldschmidt, Michael O'Dwyer, Aurore Perrot, Christopher P Venner, Katja Weisel, Joseph R Mace, Noopur Raje, Michel Attal, Mourad Tiab, Margaret Macro, Laurent Frenzel, Xavier Leleu, Tahamtan Ahmadi, Christopher Chiu, Jianping Wang, Rian Van Rampelbergh, Clarissa M Uhlar, Rachel Kobos, Ming Qi, Saad Z Usmani, MAIA Trial Investigators, Ross Baker, Jay Hocking, Cindy Lee Huey-Shin, Wojciech Janowski, Peter Mollee, Hang Quach, Sundreswran Ramanathan, William Renwick, Nicholas Wickham, Michael Fillitz, Richard Greil, Eberhard Gunsilius, Maria-Theresa Krauth, Daniel Lechner, Jo Caers, Michel Delforge, Alain Kentos, Nizar Bahlis, Susan Fox, Genevieve Gallagher, Emilie Lemieux Blanchard, Michael Sebag, Suzanne Trudel, Christopher Venner, Darrell White, Niels Abildgaard, Niels Frost Andersen, Torben Plesner, Olivier Allangba, Carla Araujo, Bertrand Arnulf, Michel Attal, Karim Belhadj-Merzoug, Lotfi Benboubker, Riad Benramdane, Malek Bouketouche, Emmanuelle Bourgeois, Didier Bouscary, Denis Caillot, Carine Chaleteix, Sylvain Choquet, Olivier Decaux, Hélène Demarquette, Mamoun Dib, Jean-Claude Eisenmann, Thierry Facon, Cecile Fohrer-Sonntag, Laurent Frenzel, Laurent Garderet, Pascal Godmer, Denis Guyotat, Cyrille Hulin, Arnaud Jaccard, Lionel Karlin, Brigitte Kolb, Xavier Leleu, Pascal Lenain, Margaret Macro, Philippe Moreau, Pierre Morel, Frederique Orsini-Piocelle, Brigitte Pegourie, Aurore Perrot, Valentine Richez, Sophie Rigaudeau, Philippe Rodon, Laurence Sanhes, Anne-Marie Stoppa, Alexia Thannberger, Mourad Tiab, Laure Vincent, Eric Voog, Charles Zarnitsky, Walter Aulitzky, Jan Dürig, Hartmut Goldschmidt, Manfred Hensel, Christian Junghanss, Martine Klausmann, Jurgen Krauter, Helfried-Christoph Mayr, Markus Munder, Christoph Röllig, Anja Rueckert, Nathalie Schub, Jörg Thomalla, Ivana von Metzler, Mohammed Wattad, Katja Weisel, Mark Coyne, Michael O'Dwyer, Irit Avivi, Dina Ben-Yehuda, Meir Preis, Orit Sofer, Celia Suriu, Iuliana Vaxman, Alberto Bosi, Tommaso Caravita Di Toritto, Nicola Giuliani, Mario Petrini, Aart Beeker, Simo Brada, Annemiek Broijl, Cecilie Blimark, Max Flogegard, Markus Hansson, Conny Karlsson, Birgitta Lauri, Hareth Nahi, Supratik Basu, Julie Blundell, Jamie Cavenagh, Jim Cavet, Gordon Cook, Hannah Hunter, Matthew Jenner, Jindriska Lindsay, Gordon Marron, Neil Rabin, Karthik Ramasamy, Alberto Rocci, Jane Tighe, Cathy Williams, Richy Agajanian, Homam Alkaied, Maqsood Amjad, Bertrand Anz 3rd, Armando Armas, Sunil Babu, Jesus Berdeja, Divaya Bhutani, Warren Brenner, Asher Chanan-Khan, Ajai Chari, Chakra Chaualgain, Arvind Chaudhry, Franklin Chen, Wilfred De La Cruz, David Drew, Brian Erikson, A Eli Gabayan, Nashat Gabrail, Eugenio Galindo, Mark Goldstein, Vincent Hansen, Jainulabdeen Ifthikharuddin, Nalini Janakiraman, Anand Karnat, Dean Kirkel, Mark Knapp, Mehmet Kocoglu, Shaji Kumar, Charles Kuzma, DeQuincy Lewis, Edward Libby, Scott Lunin, Matthew Lunning, Joseph Mace, Salman Malad, Kelly McCaul, Carole Miller, Michael Moore, Ajay Nooka, Robert Orlowski, Terri Parker, Warren Paroly, Asim Pati, Julio Peguero, Noopur Raje, Ashley Rosko, Santhosh Sadashiv, Ruben Saez, Alfred Saleh, Steven Schuster, Jaswinder Singh, Harry Staszewski, Don Stevens, Keith Stockerl-Goldstein, Bradley Sumrall, Saad Usmani, Jason Valent, David Weng, Charles Yen, Thierry Facon, Shaji Kumar, Torben Plesner, Robert Z Orlowski, Philippe Moreau, Nizar Bahlis, Supratik Basu, Hareth Nahi, Cyrille Hulin, Hang Quach, Hartmut Goldschmidt, Michael O'Dwyer, Aurore Perrot, Christopher P Venner, Katja Weisel, Joseph R Mace, Noopur Raje, Michel Attal, Mourad Tiab, Margaret Macro, Laurent Frenzel, Xavier Leleu, Tahamtan Ahmadi, Christopher Chiu, Jianping Wang, Rian Van Rampelbergh, Clarissa M Uhlar, Rachel Kobos, Ming Qi, Saad Z Usmani, MAIA Trial Investigators, Ross Baker, Jay Hocking, Cindy Lee Huey-Shin, Wojciech Janowski, Peter Mollee, Hang Quach, Sundreswran Ramanathan, William Renwick, Nicholas Wickham, Michael Fillitz, Richard Greil, Eberhard Gunsilius, Maria-Theresa Krauth, Daniel Lechner, Jo Caers, Michel Delforge, Alain Kentos, Nizar Bahlis, Susan Fox, Genevieve Gallagher, Emilie Lemieux Blanchard, Michael Sebag, Suzanne Trudel, Christopher Venner, Darrell White, Niels Abildgaard, Niels Frost Andersen, Torben Plesner, Olivier Allangba, Carla Araujo, Bertrand Arnulf, Michel Attal, Karim Belhadj-Merzoug, Lotfi Benboubker, Riad Benramdane, Malek Bouketouche, Emmanuelle Bourgeois, Didier Bouscary, Denis Caillot, Carine Chaleteix, Sylvain Choquet, Olivier Decaux, Hélène Demarquette, Mamoun Dib, Jean-Claude Eisenmann, Thierry Facon, Cecile Fohrer-Sonntag, Laurent Frenzel, Laurent Garderet, Pascal Godmer, Denis Guyotat, Cyrille Hulin, Arnaud Jaccard, Lionel Karlin, Brigitte Kolb, Xavier Leleu, Pascal Lenain, Margaret Macro, Philippe Moreau, Pierre Morel, Frederique Orsini-Piocelle, Brigitte Pegourie, Aurore Perrot, Valentine Richez, Sophie Rigaudeau, Philippe Rodon, Laurence Sanhes, Anne-Marie Stoppa, Alexia Thannberger, Mourad Tiab, Laure Vincent, Eric Voog, Charles Zarnitsky, Walter Aulitzky, Jan Dürig, Hartmut Goldschmidt, Manfred Hensel, Christian Junghanss, Martine Klausmann, Jurgen Krauter, Helfried-Christoph Mayr, Markus Munder, Christoph Röllig, Anja Rueckert, Nathalie Schub, Jörg Thomalla, Ivana von Metzler, Mohammed Wattad, Katja Weisel, Mark Coyne, Michael O'Dwyer, Irit Avivi, Dina Ben-Yehuda, Meir Preis, Orit Sofer, Celia Suriu, Iuliana Vaxman, Alberto Bosi, Tommaso Caravita Di Toritto, Nicola Giuliani, Mario Petrini, Aart Beeker, Simo Brada, Annemiek Broijl, Cecilie Blimark, Max Flogegard, Markus Hansson, Conny Karlsson, Birgitta Lauri, Hareth Nahi, Supratik Basu, Julie Blundell, Jamie Cavenagh, Jim Cavet, Gordon Cook, Hannah Hunter, Matthew Jenner, Jindriska Lindsay, Gordon Marron, Neil Rabin, Karthik Ramasamy, Alberto Rocci, Jane Tighe, Cathy Williams, Richy Agajanian, Homam Alkaied, Maqsood Amjad, Bertrand Anz 3rd, Armando Armas, Sunil Babu, Jesus Berdeja, Divaya Bhutani, Warren Brenner, Asher Chanan-Khan, Ajai Chari, Chakra Chaualgain, Arvind Chaudhry, Franklin Chen, Wilfred De La Cruz, David Drew, Brian Erikson, A Eli Gabayan, Nashat Gabrail, Eugenio Galindo, Mark Goldstein, Vincent Hansen, Jainulabdeen Ifthikharuddin, Nalini Janakiraman, Anand Karnat, Dean Kirkel, Mark Knapp, Mehmet Kocoglu, Shaji Kumar, Charles Kuzma, DeQuincy Lewis, Edward Libby, Scott Lunin, Matthew Lunning, Joseph Mace, Salman Malad, Kelly McCaul, Carole Miller, Michael Moore, Ajay Nooka, Robert Orlowski, Terri Parker, Warren Paroly, Asim Pati, Julio Peguero, Noopur Raje, Ashley Rosko, Santhosh Sadashiv, Ruben Saez, Alfred Saleh, Steven Schuster, Jaswinder Singh, Harry Staszewski, Don Stevens, Keith Stockerl-Goldstein, Bradley Sumrall, Saad Usmani, Jason Valent, David Weng, Charles Yen
Abstract
Background: Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population.
Methods: We randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival.
Results: At a median follow-up of 28.0 months, disease progression or death had occurred in 240 patients (97 of 368 patients [26.4%] in the daratumumab group and 143 of 369 patients [38.8%] in the control group). The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P<0.001). The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P<0.001). A total of 24.2% of the patients in the daratumumab group, as compared with 7.3% of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells) (P<0.001). The most common adverse events of grade 3 or 4 were neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%).
Conclusions: Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among those who received lenalidomide and dexamethasone alone. A higher incidence of neutropenia and pneumonia was observed in the daratumumab group. (Funded by Janssen Research and Development; MAIA ClinicalTrials.gov number, NCT02252172.).
Copyright © 2019 Massachusetts Medical Society.
Figures
Source: PubMed