Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myélome (IFM)

• Published in: Blood 2010-01, Vol.115 (1), p.32-37
• Main Authors: Roussel, Murielle, Moreau, Philippe, Huynh, Anne, Mary, Jean-Yves, Danho, Clotaire, Caillot, Denis, Hulin, Cyrille, Fruchart, Christophe, Marit, Gérald, Pégourié, Brigitte, Lenain, Pascal, Araujo, Carla, Kolb, Brigitte, Randriamalala, Edouard, Royer, Bruno, Stoppa, Anne-Marie, Dib, Mammoun, Dorvaux, Véronique, Garderet, Laurent, Mathiot, Claire, Avet-Loiseau, Hervé, Harousseau, Jean-Luc, Attal, Michel, Intergroupe Francophone du Myélome (IFM)
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Boronic Acids - adverse effects; Boronic Acids - therapeutic use; Bortezomib; Case-Control Studies; Demography; Disease Progression; Dose-Response Relationship, Drug; Female; France; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Melphalan - administration & dosage; Melphalan - adverse effects; Melphalan - therapeutic use; Middle Aged; Multiple Myeloma - drug therapy; Pyrazines - adverse effects; Pyrazines - therapeutic use; Stem Cell Transplantation; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-06-229658

Autologous stem cell transplantation (ASCT) is recommended for younger patients with newly diagnosed multiple myeloma. Achieving complete response (CR) or at least very good partial response (VGPR) is a major prognostic factor for survival with 20% to 30% of patients achieving CR after ASCT. Bortezomib has shown synergistic effects with melphalan and no prolonged hematologic toxicity. In this Intergroupe Francophone du Myélome (IFM) phase 2 study, 54 untreated patients were enrolled between July and December 2007 to receive bortezomib (1 mg/m2 × 4) and melphalan (200 mg/m2) as conditioning regimen (Bor-HDM). Overall, 70% of patients achieved at least VGPR, including 17 patients with CR (32%) after ASCT. No toxic deaths were observed. Bortezomib did not increase hematologic toxicity. Only 1 grade 3 to 4 peripheral neuropathy was reported. A matched control analysis was conducted comparing our cohort with patients from the IFM 2005-01 trial (HDM alone). Patients were matched for response to induction therapy and type of induction: CR was higher in the Bor-HDM group (35% vs 11%; P = .001), regardless of induction therapy. These results suggest that Bor-HDM is a safe and promising conditioning regimen. Randomized studies are needed to assess whether this conditioning regimen is superior to HDM alone. This trial was registered at www.clinicaltrials.gov as NCT00642395.