Bortezomib and high-dose melphalan conditioning regimen in frontline multiple myeloma: an IFM randomized phase 3 study

• Published in: Blood Vol. 139; no. 18; pp. 2747 - 2757
• Main Authors: Roussel, Murielle, Lauwers-Cances, Valérie, Macro, Margaret, Leleu, Xavier, Royer, Bruno, Hulin, Cyrille, Karlin, Lionel, Perrot, Aurore, Touzeau, Cyrille, Chrétien, Marie-Lorraine, Rigaudeau, Sophie, Dib, Mamoun, Nicolas-Virelizier, Emmanuelle, Escoffre-Barbe, Martine, Belhadj, Karim, Mariette, Clara, Stoppa, Anne-Marie, Araujo, Carla, Doyen, Chantal, Fontan, Jean, Kolb, Brigitte, Garderet, Laurent, Brechignac, Sabine, Malfuson, Jean-Valère, Jaccard, Arnaud, Lenain, Pascal, Borel, Cécile, Hebraud, Benjamin, Benbrahim, Omar, Dorvaux, Véronique, Manier, Salomon, Augeul-Meunier, Karine, Vekemans, Marie-Christiane, Randriamalala, Edouard, Chaoui, Driss, Caers, Jo, Chaleteix, Carine, Benboubker, Lofti, Vincent, Laure, Glaisner, Sylvie, Zunic, Patricia, Slama, Borhane, Eveillard, Jean-Richard, Humbrecht-Kraut, Catherine, Morel, Véronique, Mineur, Philippe, Eisenmann, Jean-Claude, Demarquette, Hélène, Richez, Valentine, Vignon, Marguerite, Caillot, Denis, Facon, Thierry, Moreau, Philippe, Colin, Anne-Laurène, Olivier, Pascale, Wuilleme, Soraya, Avet-Loiseau, Hervé, Corre, Jill, Attal, Michel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.05.2022
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bortezomib - adverse effects; Humans; Melphalan - adverse effects; Multiple Myeloma - drug therapy; Multiple Myeloma - etiology; Transplantation, Autologous
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2021014635

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. •The Bor-HDM (200 mg/m2) conditioning regimen is not superior to HDM alone in de novo multiple myeloma.•HDM (200 mg/m2) remains the standard-of-care conditioning for transplantation in multiple myeloma. [Display omitted]