[en] High-dose melphalan (HDM) and transplantation are recommended for eligible patients with multiple myeloma. No other conditioning regimen has proven to be more effective and/or safer. We previously reported in a phase 2 study that bortezomib can safely and effectively be combined with HDM (Bor-HDM), with a 32% complete response (CR) rate after transplantation. These data supported a randomized phase 3 trial. Randomization was stratified according to risk and response to induction: 300 patients were enrolled, and 154 were allocated to the experimental arm (ie, arm A) with bortezomib (1 mg/m2 intravenously [IV]) on days -6, -3, +1, and +4 and melphalan (200 mg/m2 IV) on day -2. The control arm (ie, arm B) consisted of HDM alone (200 mg/m2 IV). There were no differences in stringent CR + CR rates at day 60 posttransplant (primary end point): 22.1% in arm A vs 20.5% in arm B (P = .844). There were also no differences in undetectable minimum residual disease rates: 41.3% vs 39.4% (P = .864). Median progression-free survival was 34.0 months for arm A vs 29.6 months for arm B (adjusted HR, 0.82; 95% CI, 0.61-1.13; P = .244). The estimated 3-year overall survival was 89.5% in both arms (hazard ratio, 1.28; 95% CI, 0.62-2.64; P = .374). Sixty-nine serious adverse events occurred in 18.7% of Bor-HDM-treated patients (vs 13.1% in HDM-treated patients). The proportion of grade 3/4 AEs was similar within the 2 groups (72.0% vs 73.1%), mainly (as expected) blood and gastrointestinal disorders; 4% of patients reported grade 3/4 or painful peripheral neuropathy in arm A (vs 1.5% in arm B). In this randomized phase 3 study, a conditioning regimen with Bor-HDM did not improve efficacy end points or outcomes compared with HDM alone. The original trial was registered at www.clinicaltrials.gov as #NCT02197221.
Disciplines :
Hematology
Author, co-author :
Roussel, Murielle ; Service d'hématologie, Centre Hospitalo-universitaire (CHU) de Toulouse, Institut ; USMR, Centre Hospitalo-universitaire (CHU) de Toulouse, Toulouse, France.
Lauwers-Cances, Valérie; USMR, Centre Hospitalo-universitaire (CHU) de Toulouse, Toulouse, France.
Macro, Margaret; Centre Hospitalo-universitaire (CHU) Côte de Nacre, Caen, France.
Leleu, Xavier; Centre Hospitalo-universitaire (CHU) La Mileterie, INSERM CIC 1402, Poitiers,
Royer, Bruno; Centre Hospitalo-universitaire (CHU) Amiens sud, Amiens, France. ; Hôpital St Louis, Paris, France.
Hulin, Cyrille; Centre Hospitalo-universitaire (CHU) Haut Lévêque, Bordeaux, France.
Karlin, Lionel; Hospices Civils de Lyon, Pierre Bénite, France.
Perrot, Aurore ; Service d'hématologie, Centre Hospitalo-universitaire (CHU) de Toulouse, Institut ; USMR, Centre Hospitalo-universitaire (CHU) de Toulouse, Toulouse, France. ; Centre Hospitalo-universitaire (CHU) Côte de Nacre, Caen, France. ; Centre Hospitalo-universitaire (CHU) La Mileterie, INSERM CIC 1402, Poitiers, ; Centre Hospitalo-universitaire (CHU) Amiens sud, Amiens, France. ; Centre Hospitalo-universitaire (CHU) Haut Lévêque, Bordeaux, France. ; Hospices Civils de Lyon, Pierre Bénite, France. ; Centre Hospitalo-universitaire (CHU), Vandoeuvre Les Nancy, France.
Touzeau, Cyrille; Centre Hospitalo-universitaire (CHU) Hôtel Dieu, Nantes, France.
Chrétien, Marie-Lorraine; Centre Hospitalo-universitaire (CHU), Dijon, France.
Rigaudeau, Sophie; CH A. Mignot, Versailles, France.
Dib, Mamoun; Hôpital du Bocage, Angers, France.
Nicolas-Virelizier, Emmanuelle; Centre Léon Bérard, Lyon, France.
Escoffre-Barbe, Martine; Centre Hospitalo-universitaire (CHU) Pontchaillou, Rennes, France.
Belhadj, Karim; Centre Hospitalo-universitaire (CHU) Henri Mondor, Créteil, France.
Mariette, Clara; Hôpital A. Michallon, Grenoble, France.
Stoppa, Anne-Marie; Institut Paoli Calmettes, Marseille, France.
Araujo, Carla; Centre Hospitalier de la côte basque, Bayonne, France.
Doyen, Chantal; Centre Hospitalo-universitaire (CHU) UCL Namur site Godinne, Yvoir, Belgium.
Fontan, Jean; Centre Hospitalo-universitaire (CHU), Besançon, France.
Kolb, Brigitte; Hopital Robert Debré, Reims Cedex, France.
Garderet, Laurent; Hôpital Saint Antoine, Paris, France. ; Hematology Hôpital Avicenne, Bobigny, France.
Brechignac, Sabine; Hematology Hôpital Avicenne, Bobigny, France.
Malfuson, Jean-Valère; Hôpital d'instruction des armées Percy, Clamart, France.
Jaccard, Arnaud; Centre Hospitalo-universitaire (CHU) Dupuytren, Limoges, France.
Lenain, Pascal; Centre Henri Becquerel, Rouen, France.
Borel, Cécile; Service d'hématologie, Centre Hospitalo-universitaire (CHU) de Toulouse, Institut
Hebraud, Benjamin; Service d'hématologie, Centre Hospitalo-universitaire (CHU) de Toulouse, Institut
Benbrahim, Omar; Hôpital La Source, Orléans, France.
Dorvaux, Véronique; Hôpital Notre Dame de Bon Secours, Metz-Thionville, France.
Manier, Salomon; CHRU-Hôpital Claude Huriez, Lille, France.
Augeul-Meunier, Karine; Institut De Cancérologie De La Loire St Priest-en-Jarez.
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