Busulfan 12 mg/kg plus melphalan 140 mg/m2 versus melphalan 200 mg/m2 as conditioning regimens for autologous transplantation in newly diagnosed multiple myeloma patients included in the PETHEMA/GEM2000 study
Juan José Lahuerta, Maria Victoria Mateos, Joaquin Martínez-López, Carlos Grande, Javier de la Rubia, Laura Rosiñol, Anna Sureda, José García-Laraña, Joaquín Díaz-Mediavilla, Miguel T Hernández-García, Dolores Carrera, Joan Besalduch, Felipe de Arriba, Albert Oriol, Lourdes Escoda, Javier García-Frade, Concepción Rivas-González, Adrían Alegre, Joan Bladé, Jesús F San Miguel, Grupo Español de MM and Programa para el Estudio de la Terapéutica en Hemopatía Maligna Cooperative Study Groups, J J Lahuerta, J F San Miguel, A Sureda, J De la Rubia, J García-Laraña, R Martínez- Martínez, M T Hernández-García, D Carrera, J Besalduch, F de Arriba, J M Ribera, L Escoda, B Hernández-Ruíz, J García Frade, C Rivas González, A Alegre, L Palomera, M L Martín-Mateos, R García-Boyero, F Prosper, F Casado, F J Fernández Calvo, S Gardella, M J Terol, J C Gómez-García, P Ribas García, E Monzó, A León Lara, J L Bello, J D González San Miguel, J M Ojanguren, E Abella, M Subirà, J A Soler, P Sánchez-Godoy, I Pérez-Fernández, C Poderos, E Conde García, J C García Ruíz, L Rodríguez Fernández, M Callis De Nadal, J Galende del Canto, A Alcalá Muñoz, L García Alonso, K Pérez Equiza, M Vargas Pabón, M J Fernández Llavador, P Galán, M J Busto, J Serena, C Burgaleta, J Ibañez, F Solano, A Barez, J Bargay, A Modolell, J M Hernández-Martín, I Navarro, R Ferrer, A Altes, R Butrón, R Herraez, J A Hernández Ribas, F Ortega Rivas, L Font Ferré, M Orero, P Lorente, A Martín, Juan José Lahuerta, Maria Victoria Mateos, Joaquin Martínez-López, Carlos Grande, Javier de la Rubia, Laura Rosiñol, Anna Sureda, José García-Laraña, Joaquín Díaz-Mediavilla, Miguel T Hernández-García, Dolores Carrera, Joan Besalduch, Felipe de Arriba, Albert Oriol, Lourdes Escoda, Javier García-Frade, Concepción Rivas-González, Adrían Alegre, Joan Bladé, Jesús F San Miguel, Grupo Español de MM and Programa para el Estudio de la Terapéutica en Hemopatía Maligna Cooperative Study Groups, J J Lahuerta, J F San Miguel, A Sureda, J De la Rubia, J García-Laraña, R Martínez- Martínez, M T Hernández-García, D Carrera, J Besalduch, F de Arriba, J M Ribera, L Escoda, B Hernández-Ruíz, J García Frade, C Rivas González, A Alegre, L Palomera, M L Martín-Mateos, R García-Boyero, F Prosper, F Casado, F J Fernández Calvo, S Gardella, M J Terol, J C Gómez-García, P Ribas García, E Monzó, A León Lara, J L Bello, J D González San Miguel, J M Ojanguren, E Abella, M Subirà, J A Soler, P Sánchez-Godoy, I Pérez-Fernández, C Poderos, E Conde García, J C García Ruíz, L Rodríguez Fernández, M Callis De Nadal, J Galende del Canto, A Alcalá Muñoz, L García Alonso, K Pérez Equiza, M Vargas Pabón, M J Fernández Llavador, P Galán, M J Busto, J Serena, C Burgaleta, J Ibañez, F Solano, A Barez, J Bargay, A Modolell, J M Hernández-Martín, I Navarro, R Ferrer, A Altes, R Butrón, R Herraez, J A Hernández Ribas, F Ortega Rivas, L Font Ferré, M Orero, P Lorente, A Martín
Abstract
Background: The aim of this study was to compare the long-term safety and efficacy of oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) and melphalan 200 mg/m(2) as conditioning regimens for autologous stem cell transplantation in newly diagnosed patients with multiple myeloma in the GEM2000 study.
Design and methods: The first 225 patients received oral busulfan 12 mg/kg plus melphalan 140 mg/m(2); because of a high frequency of veno-occlusive disease, the protocol was amended and a further 542 patients received melphalan 200 mg/m(2).
Results: Engraftment and hospitalization times were similar in both groups. Oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) resulted in higher transplant-related mortality (8.4% versus 3.5%; P=0.002) due to the increased frequency of veno-occlusive disease in this group. Response rates were similar in both arms. With respective median follow-ups of 72 and 47 months, the median progression-free survival was significantly longer with busulfan plus melphalan (41 versus 31 months; P=0.009), although survival was similar to that in the melphalan 200 mg/m(2) group. However, access to novel agents as salvage therapy after relapse/progression was significantly lower for patients receiving busulfan plus melphalan (43%) than for those receiving melphalan 200 mg/m(2) (58%; P=0.01).
Conclusions: Conditioning with oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) was associated with longer progression-free survival but equivalent survival to that achieved with melphalan 200 mg/m(2) but this should be counterbalanced against the higher frequency of veno-occlusive disease-related deaths. This latter fact together with the limited access to novel salvage therapies in patients conditioned with oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) may explain the absence of a survival difference. Oral busulfan was used in the present study; use of the intravenous formulation may reduce toxicity and result in greater efficacy, and warrants further investigation in myeloma patients. (Clinicaltrials.gov identifier: NCT00560053).
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Source: PubMed