Annals of Oncology Advance Access originally published online on May 22, 2009
Annals of Oncology 2009 20(8):1303-1317; doi:10.1093/annonc/mdn796
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The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network
1 Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra University Hospital, Athens, Greece
2 Department of Hematology, Faculty of Medicine Imperial College London, London, UK
3 Department of Hematology and Oncology, Charité—Universitätsmedizin Berlin, Berlin, Germany
4 Unit of Bone Biology, Division of Clinical Sciences (South), University of Sheffield Medical School, Sheffield, UK
5 Department of Hematology, University Hospital of Salamanca and Centro de Investigación del Cáncer, University of Salamanca, Salamanca, Spain
6 Division of Hematology, San Giovanni Battista Hospital, Università di Torino, Turin, Italy
7 Department of Hematology, Pinderfields Hospital, Mid-Yorkshire NHS Trust and University of Leeds, Wakefield, UK
8 Department of Hematology, Hospital Clinic I Provincial, Barcelona
9 Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Barcelona, Spain
10 Institute of Hematology and Medical Oncology "Seràgnoli", Bologna University School of Medicine, S.Orsola's University Hospital, Bologna, Italy
11 Department of Hematology, University Hospital Leuven, Leuven, Belgium
12 Service des Maladies du Sang, Hôpital Claude Huriez, CHRU, Lille
13 Department of Clinical Hematology, Centre Hospitalier Universitaire de Caen, Caen, France
14 Department of Hematology, St Olavs Hospital/NTNU, Trondheim, Norway
15 Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands
* Correspondence to: Dr E. Terpos, Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra University Hospital, 5 Marathonomahon Street, Drossia, 14572, Athens, Greece. Tel: +30-210-7463803; Fax: +30-210-7464676; E-mail: eterpos{at}hotmail.com
Background: Bisphosphonates (BPs) prevent, reduce, and delay multiple myeloma (MM)-related skeletal complications. Intravenous pamidronate and zoledronic acid, and oral clodronate are used for the management of MM bone disease. The purpose of this paper is to review the current evidence for the use of BPs in MM and provide European Union-specific recommendations to support the clinical practice of treating myeloma bone disease.
Design and methods: An interdisciplinary, expert panel of specialists on MM and myeloma-related bone disease convened for a face-to-face meeting to review and assess the evidence and develop the recommendations. The panel reviewed and graded the evidence available from randomized clinical trials, clinical practice guidelines, and the body of published literature. Where published data were weak or unavailable, the panel used their own clinical experience to put forward recommendations based solely on their expert opinions.
Results: The panel recommends the use of BPs in MM patients suffering from lytic bone disease or severe osteoporosis. Intravenous administration may be preferable; however, oral administration can be considered for patients unable to make hospital visits. Dosing should follow approved indications with adjustments if necessary. In general, BPs are well tolerated, but preventive steps should be taken to avoid renal impairment and osteonecrosis of the jaw (ONJ). The panel agrees that BPs should be given for 2 years, but this may be extended if there is evidence of active myeloma bone disease. Initial therapy of ONJ should include discontinuation of BPs until healing occurs. BPs should be restarted if there is disease progression.
Conclusions: BPs are an essential component of MM therapy for minimizing skeletal morbidity. Recent retrospective data indicate that a modified dosing regimen and preventive measures can greatly reduce the incidence of ONJ.
Key words: bisphosphonates, multiple myeloma, osteonecrosis of the jaw, recommendations, renal impairment
Received for publication September 2, 2008. Revision received December 2, 2008. Accepted for publication December 19, 2008.
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