High-dose busulfan-melphalan vs melphalan and reinforced VRD for newly diagnosed multiple myeloma: a phase 3 GEM trial

In retrospective studies, autologous stem cell transplantation (ASCT) conditioning with intravenous busulfan and melphalan (BUMEL) led to longer progression-free survival (PFS) than melphalan alone (MEL200). We compared long-term outcomes of BUMEL vs MEL200 in the context of intensified bortezomib, lenalidomide, and dexamethasone (VRD) induction and consolidation therapies. GEM12 was a phase 3 trial for patients with newly diagnosed multiple myeloma (NDMM) eligible for ASCT including 6 reinforced VRD cycles followed by ASCT conditioned with BUMEL or MEL200 and 2 VRD consolidation cycles. The primary end point was PFS. Subgroup analyses were based on International Staging System (ISS) stages and high-risk genetic abnormalities. Patients were randomized with an open-label 2 × 2 factorial design and 1:1:1:1 allocation ratio to ensure the balance between the GEM12 and the subsequent phase 3 GEM14 trial. Between 2013 and 2015, 458 patients were randomized (BUMEL, n = 230; MEL200, n = 228). The 10⁻⁶ MRD-negative rate was 63%, 68% for BUMEL vs 58% for MEL200 (odds ratio, 1.51; P = .035). The median PFS was 89 months for BUMEL and 73.1 for MEL200 (hazard ratio, 0.89 [95% confidence interval, 0.70-1.14]; P = .3). BUMEL showed benefit for patients with ISS stages II or III, t(14;16), and del(1p). For subcohorts ISS stages II or III treated with BUMEL and ISS I treated with MEL200 the median PFS was 96.5 months (95% confidence interval, 76 to not estimable). No safety concerns were observed. After a median follow-up of 8.4 years, GEM2012 demonstrated one of the longest PFS values reported in patients with NDMM, with significant differences favoring BUMEL in advanced ISS stages. The trial was registered at www.ClinicalTrials.gov as #NCT01916252 and at European Union Drug Regulating Authorities Clinical Trials as EudraCT 2012-005683-10.

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Journal
Blood
Published
2025-06-11
DOI
https://doi.org/10.1182/blood.2025028313
Citations
4
Primary Topic
Multiple Myeloma Research and Treatments
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article
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7.08
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article

High-dose busulfan-melphalan vs melphalan and reinforced VRD for newly diagnosed multiple myeloma: a phase 3 GEM trial

Enrique M. Ocio, Yolanda González‐Montes, Laura Rosiñol, Juan José Lahuerta et al.
4 citations
Blood
Multiple Myeloma Research and Treatments
7.08
article

High-dose busulfan-melphalan vs melphalan and reinforced VRD for newly diagnosed multiple myeloma: a phase 3 GEM trial

Enrique M. Ocio, Yolanda González‐Montes, Laura Rosiñol, Juan José Lahuerta, Ana Jiménez Ubieto, María Esther González-García, María‐Victoria Mateos, Javier de la Rubia, Joaquín Martínez‐López, Joan Bargay, José-María Arguiñano, Javier de la Cruz, María‐Teresa Cedena, Noemí Puig, Norma C. Gutiérrez, Albert Oriol, Bruno Paiva, Felipe Casado Montero, Valentín Cabañas, Estrella Carrillo‐Cruz, Miguel‐Teodoro Hernández, Anna Sureda, Isabel Krsnik, Luis Palomera, Paula Rodríguez‐Otero, Marı́a José Calasanz, Rafael Alonso Fernández, Rafael Ríos, Joan Bladé, Rafael Martínez-Martinez, Manuela Fernández, María‐Jesús Blanchard
article en
4 citations

Abstract

In retrospective studies, autologous stem cell transplantation (ASCT) conditioning with intravenous busulfan and melphalan (BUMEL) led to longer progression-free survival (PFS) than melphalan alone (MEL200). We compared long-term outcomes of BUMEL vs MEL200 in the context of intensified bortezomib, lenalidomide, and dexamethasone (VRD) induction and consolidation therapies. GEM12 was a phase 3 trial for patients with newly diagnosed multiple myeloma (NDMM) eligible for ASCT including 6 reinforced VRD cycles followed by ASCT conditioned with BUMEL or MEL200 and 2 VRD consolidation cycles. The primary end point was PFS. Subgroup analyses were based on International Staging System (ISS) stages and high-risk genetic abnormalities. Patients were randomized with an open-label 2 × 2 factorial design and 1:1:1:1 allocation ratio to ensure the balance between the GEM12 and the subsequent phase 3 GEM14 trial. Between 2013 and 2015, 458 patients were randomized (BUMEL, n = 230; MEL200, n = 228). The 10⁻⁶ MRD-negative rate was 63%, 68% for BUMEL vs 58% for MEL200 (odds ratio, 1.51; P = .035). The median PFS was 89 months for BUMEL and 73.1 for MEL200 (hazard ratio, 0.89 [95% confidence interval, 0.70-1.14]; P = .3). BUMEL showed benefit for patients with ISS stages II or III, t(14;16), and del(1p). For subcohorts ISS stages II or III treated with BUMEL and ISS I treated with MEL200 the median PFS was 96.5 months (95% confidence interval, 76 to not estimable). No safety concerns were observed. After a median follow-up of 8.4 years, GEM2012 demonstrated one of the longest PFS values reported in patients with NDMM, with significant differences favoring BUMEL in advanced ISS stages. The trial was registered at www.ClinicalTrials.gov as #NCT01916252 and at European Union Drug Regulating Authorities Clinical Trials as EudraCT 2012-005683-10.

BloodVol. 146(15)
Universidad de Cantabria (ES), Consejo Superior de Investigaciones Científicas (ES), Universidad de Salamanca (ES), Catalan Institute for Water Research (ES), Hospital Universitario de Canarias (ES), Hospital Clínico San Carlos (ES), Hospital Universitari i Politècnic La Fe (ES), Research Institute Hospital 12 de Octubre (ES), Hospital Son Llatzer (ES), Clínica Girona (ES), Complejo Hospitalario de Navarra (ES), Complejo Hospitalario de Salamanca (ES), Marqués de Valdecilla University Hospital (ES), Hospital Universitario 12 De Octubre (ES), Hospital Universitario Puerta de Hierro Majadahonda (ES), Institut Català d'Oncologia (ES), Instituto de Investigación Marqués de Valdecilla (ES), Hospital Clínic de Barcelona (ES), Hospital Universitario Virgen de las Nieves (ES), HM Hospitales (ES), Health Research Institute of the Balearic Islands (ES), Instituto de Investigación Biomédica de Salamanca (ES), Clinica Universidad de Navarra (ES), Hospital Clínico Universitario Lozano Blesa (ES), Centro de Investigación del Cáncer (ES), Duran i Reynals Hospital (ES), Instituto Murciano de Investigación Biosanitaria (ES), Hospital Universitario De Cabueñes (ES), Hospital Universitario Virgen de la Arrixaca (ES), Hospital Universitario Virgen del Rocío (ES), Centro de Investigación Biomédica en Red de Cáncer (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Hospital Universitario Ramón y Cajal (ES), Universidad de Navarra (ES)
Openalex Percentile: Top 3%
Multiple Myeloma Research and Treatments
7.08
DOISourceOpenAlex
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