title: Effects of single-agent bortezomib as post-transplant consolidation therapy on multiple myeloma-related bone disease: a randomized phase II study.
abstract: This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles of bortezomib 1·6 mg/m2intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent-to-treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End-of-treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression-free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival.
authors.affiliation: Department of Haematology, Oncology, and Bone Marrow Transplantation, Universitaetsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Orhan
authors.identifier: 0000-0001-8645-9573
authors.initials: O
authors.lastname: Sezer
authors.affiliation: Department of Medicine, Ankara University, Ankara, Turkey.
authors.forename: Meral
authors.initials: M
authors.lastname: Beksac
authors.affiliation: Department of Haemato-oncology, University Hospital Ostrava, Ostrava, Czech Republic.|Faculty of Medicine, University Ostrava, Ostrava, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Hajek
authors.affiliation: Department of Haematology, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Gülsan
authors.initials: G
authors.lastname: Sucak
authors.affiliation: Department of Haematology, Izmir Medical Park Private Hospital, Izmir, Turkey.
authors.forename: Seckin
authors.initials: S
authors.lastname: Cagirgan
authors.affiliation: Department of Haematology, Medical University Clinic, Medical University of Graz, Graz, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Linkesch
authors.affiliation: Department of Haematology, Eskisehir Osmangazi University, Eskisehir, Turkey.
authors.forename: Olga
authors.initials: O
authors.lastname: Meltem Akay
authors.affiliation: Department of Haematology, Eskisehir Osmangazi University, Eskisehir, Turkey.|Oncologic Sciences, Anadolu Health Centre, Kocaeli, Turkey.
authors.forename: Zafer
authors.initials: Z
authors.lastname: Gülbas
authors.affiliation: Department of Haematology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Hareth
authors.initials: H
authors.lastname: Nahi
authors.affiliation: Department of Haematology, Vejle Hospital, Vejle, Denmark.|IRS/University of Southern Denmark, Vejle, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Plesner
authors.affiliation: Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.|Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Snowden
authors.affiliation: Department of Haematology, Akdeniz University, Antalya, Turkey.
authors.forename: Ayşen
authors.initials: A
authors.lastname: Timurağaoğlu
authors.affiliation: III. Medical Dept., Klinikum Rechts der Isar, Technical University Munich, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Dechow
authors.affiliation: Department of Haematology and Oncology, LandesKrankenhaus, Feldkirch, Austria.
authors.forename: Alois
authors.initials: A
authors.lastname: Lang
authors.affiliation: Department of Internal Medicine, Marmara University, Istanbul, Turkey.
authors.forename: Tülin
authors.initials: T
authors.lastname: Tuğlular
authors.affiliation: Department of Internal Medicine I, Division of Oncology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Drach
authors.affiliation: Department of Radiology, Centre for Muscle and Bone Research, Charité - Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Armbrecht
authors.affiliation: Janssen-Cilag Pharmaceutical SACI, Athens, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Potamianou
authors.affiliation: Janssen-Cilag, Issy-les-Moulineaux, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Couturier
authors.affiliation: Janssen-Cilag AG, Zug, Switzerland.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Olie
authors.affiliation: Janssen Research & Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Feys
authors.affiliation: Janssen-Cilag, Issy-les-Moulineaux, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Allietta
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D000069286:Bortezomib / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D060830:Consolidation Chemotherapy / Q000379:methods*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010014:Osteolysis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D000069286:Bortezomib
keywords: bone; bone mineral density; bortezomib; consolidation; multiple myeloma