Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma
Lotfi Benboubker, Meletios A Dimopoulos, Angela Dispenzieri, John Catalano, Andrew R Belch, Michele Cavo, Antonello Pinto, Katja Weisel, Heinz Ludwig, Nizar Bahlis, Anne Banos, Mourad Tiab, Michel Delforge, Jamie Cavenagh, Catarina Geraldes, Je-Jung Lee, Christine Chen, Albert Oriol, Javier de la Rubia, Lugui Qiu, Darrell J White, Daniel Binder, Kenneth Anderson, Jean-Paul Fermand, Philippe Moreau, Michel Attal, Robert Knight, Guang Chen, Jason Van Oostendorp, Christian Jacques, Annette Ervin-Haynes, Hervé Avet-Loiseau, Cyrille Hulin, Thierry Facon, FIRST Trial Team, C Forsyth, P Presgrave, J Szer, S Durrant, P Campbell, P Mollee, D Coghlan, J Wellwood, P Cannell, M Prince, R Eek, N Horvath, S Harrison, W Renwick, J Thaler, A Petzer, H Kasparu, T Bauernhofer, J Meran, M Fridrik, P Balcke, H Gisslinger, R Greil, C Doyen, N Meuleman, P Pierre, M Vekemans, H Demuynck, K Wu, J Van Droogenbroeck, R Schots, F Offner, A Van de Velde, R Leblanc, A Tosikyan, C Shustik, K Song, B Lemieux, L Minuk, M Lalancette, M Cheung, M Noble, R Vanderjagt, P Desjardins, N Aucoin, G Dueck, A Yee, A Reiman, T Kouroukis, S Assouline, A Al-Tourah, J Lu, W Chen, T Liu, Z Shen, M Alexis, D Assouline, B Audhuy, I Azais, K Belhadj, R Benramdane, A Tempescul, F Boue, C Rose, J Bourhis, D Bouscary, D Caillot, P Casassus, B De Renzis, P Genet, T De Revel, M Dib, V Dorvaux, G Etienne, E Gabriel, J Eisenmann, O Fitoussi, L Garderet, M Gaspard, C Sebban, S Glaisner, I Griffoul, O Decaux, R Herbrecht, A Jaccard, H Jardel, R Kaphan, B Kolb, M Escoffre Barbe, K Laribi, P Lenain, M Macro, H Maisonneuve, S Pavy, G Marit, M Michallet, O Allangbam, L Mosser, B Pegourie, S Rigaudeau, P Rodon, J Rossi, B Royer, J Eschard, A Stoppa, E Suc, A Thyss, G Salles, J Vilque, L Voillat, E Voog, M Wetterwald, C Zarnitsky, C Junghanss, U Dührsen, R Fenk, M Rummel, H G Derigs, M Zeis, L Mügge, O Ottmann, H Ostermann, M Kropff, D Niederwieser, C Langer, C Röllig, P Panagiotidis, A Corso, N Di Renzo, R Foa, A Fragasso, L Canepa, G Martinelli, B Gamberi, M Musso, M Petrini, F Pisani, G Quarta, S Sacchi, P Tassone, A Lazzaro, F Ciceri, P Browett, K Romeril, A Butler, J Parreira, A Martins, M Herlander, C Gonçalves, J H Lee, S Yoon, H Eom, D Jo, J Kwak, H Ryoo, J Lee, S J Kim, C K Min, C Suh, K Kim, W Lee, Y Mun, H J Kim, J J Lahuerta-Palacios, J Bargay Lleonart, M S Gonzalez, A Bermudez-Rodriguez, F De Arriba de la Fuente, M Mateo-Morales, Y Gonzalez-Montes, D Hernandez-Maraver, V Clapés, F Prosper-Cardoso, G Ramírez, A Teruel Casasus, M Granell, P Giraldo-Castellano, A Echeveste-Gutierrez, L Palomera-Bernal, H Nahi, A Gruber, F Sjöö, S Leyvraz, T Pabst, D Heim, M Bargetzi, R Cathomas, S Huang, S Yeh, T Chiou, Y Ezaydi, T Littlewood, C Knechtli, G McQuaker, C Fegan, A Mehta, J Bird, J Ashcroft, M Kazmi, H Hunter, M Cook, C Crawley, S Basu, R Hall, J Seale, W Bensinger, S Coutre, V Priego, T Martin, H Kaplan, N Tirumali, S Dakhil, M Gupta, R Jacobson, D Vogl, M Moezi, D Gravenor, F Yunus, T Guthrie, F Reu, R Catchatourian, N Gabrail, J Nieva, M De la Puerta, H Ryan, Lotfi Benboubker, Meletios A Dimopoulos, Angela Dispenzieri, John Catalano, Andrew R Belch, Michele Cavo, Antonello Pinto, Katja Weisel, Heinz Ludwig, Nizar Bahlis, Anne Banos, Mourad Tiab, Michel Delforge, Jamie Cavenagh, Catarina Geraldes, Je-Jung Lee, Christine Chen, Albert Oriol, Javier de la Rubia, Lugui Qiu, Darrell J White, Daniel Binder, Kenneth Anderson, Jean-Paul Fermand, Philippe Moreau, Michel Attal, Robert Knight, Guang Chen, Jason Van Oostendorp, Christian Jacques, Annette Ervin-Haynes, Hervé Avet-Loiseau, Cyrille Hulin, Thierry Facon, FIRST Trial Team, C Forsyth, P Presgrave, J Szer, S Durrant, P Campbell, P Mollee, D Coghlan, J Wellwood, P Cannell, M Prince, R Eek, N Horvath, S Harrison, W Renwick, J Thaler, A Petzer, H Kasparu, T Bauernhofer, J Meran, M Fridrik, P Balcke, H Gisslinger, R Greil, C Doyen, N Meuleman, P Pierre, M Vekemans, H Demuynck, K Wu, J Van Droogenbroeck, R Schots, F Offner, A Van de Velde, R Leblanc, A Tosikyan, C Shustik, K Song, B Lemieux, L Minuk, M Lalancette, M Cheung, M Noble, R Vanderjagt, P Desjardins, N Aucoin, G Dueck, A Yee, A Reiman, T Kouroukis, S Assouline, A Al-Tourah, J Lu, W Chen, T Liu, Z Shen, M Alexis, D Assouline, B Audhuy, I Azais, K Belhadj, R Benramdane, A Tempescul, F Boue, C Rose, J Bourhis, D Bouscary, D Caillot, P Casassus, B De Renzis, P Genet, T De Revel, M Dib, V Dorvaux, G Etienne, E Gabriel, J Eisenmann, O Fitoussi, L Garderet, M Gaspard, C Sebban, S Glaisner, I Griffoul, O Decaux, R Herbrecht, A Jaccard, H Jardel, R Kaphan, B Kolb, M Escoffre Barbe, K Laribi, P Lenain, M Macro, H Maisonneuve, S Pavy, G Marit, M Michallet, O Allangbam, L Mosser, B Pegourie, S Rigaudeau, P Rodon, J Rossi, B Royer, J Eschard, A Stoppa, E Suc, A Thyss, G Salles, J Vilque, L Voillat, E Voog, M Wetterwald, C Zarnitsky, C Junghanss, U Dührsen, R Fenk, M Rummel, H G Derigs, M Zeis, L Mügge, O Ottmann, H Ostermann, M Kropff, D Niederwieser, C Langer, C Röllig, P Panagiotidis, A Corso, N Di Renzo, R Foa, A Fragasso, L Canepa, G Martinelli, B Gamberi, M Musso, M Petrini, F Pisani, G Quarta, S Sacchi, P Tassone, A Lazzaro, F Ciceri, P Browett, K Romeril, A Butler, J Parreira, A Martins, M Herlander, C Gonçalves, J H Lee, S Yoon, H Eom, D Jo, J Kwak, H Ryoo, J Lee, S J Kim, C K Min, C Suh, K Kim, W Lee, Y Mun, H J Kim, J J Lahuerta-Palacios, J Bargay Lleonart, M S Gonzalez, A Bermudez-Rodriguez, F De Arriba de la Fuente, M Mateo-Morales, Y Gonzalez-Montes, D Hernandez-Maraver, V Clapés, F Prosper-Cardoso, G Ramírez, A Teruel Casasus, M Granell, P Giraldo-Castellano, A Echeveste-Gutierrez, L Palomera-Bernal, H Nahi, A Gruber, F Sjöö, S Leyvraz, T Pabst, D Heim, M Bargetzi, R Cathomas, S Huang, S Yeh, T Chiou, Y Ezaydi, T Littlewood, C Knechtli, G McQuaker, C Fegan, A Mehta, J Bird, J Ashcroft, M Kazmi, H Hunter, M Cook, C Crawley, S Basu, R Hall, J Seale, W Bensinger, S Coutre, V Priego, T Martin, H Kaplan, N Tirumali, S Dakhil, M Gupta, R Jacobson, D Vogl, M Moezi, D Gravenor, F Yunus, T Guthrie, F Reu, R Catchatourian, N Gabrail, J Nieva, M De la Puerta, H Ryan
Abstract
Background: The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches.
Methods: We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT.
Results: The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P<0.001 for both comparisons). Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points, including overall survival (at the interim analysis). Overall survival at 4 years was 59% with continuous lenalidomide-dexamethasone, 56% with 18 cycles of lenalidomide-dexamethasone, and 51% with MPT. Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT (70% vs. 78%). As compared with MPT, continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events, a moderate increase in infections, and fewer second primary hematologic cancers.
Conclusions: As compared with MPT, continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. (Funded by Intergroupe, Francophone du Myélome and Celgene; FIRST ClinicalTrials.gov number, NCT00689936; European Union Drug Regulating Authorities Clinical Trials number, 2007-004823-39.).
Source: PubMed