Prophylaxe und Therapie beim multiplen Myelom und anderen tumorbedingten Knochenveränderungen

Zusammenfassung

Das multiple Myelom ist die 2. häufigste hämatologische Neoplasie und betrifft vorwiegend ältere Patienten. Ca. 90 % aller Patienten mit Myelom erleiden im Laufe ihrer Erkrankung skelettale Komplikationen wie Frakturen, Myelonkompression, Querschnittssymptomatik oder Hyperkalzämie. Für die Diagnostik dieser Knochenläsionen stehen neben dem Nativ-Röntgen auch sensitivere radiologische Verfahren wie CT, NMR und PET zur Verfügung, letztere um das Ausmaß der Osteolysen eindeutiger zu verifizieren. Zur Therapie dieser Osteolysen sind Bisphosphonate der Goldstandard; zudem die effektive MyelomTherapie unter Einschluss innovativer Substanzen, wie des Proteasominhibitors Bortezomib oder immunmodulatorischer Substanzen (IMIDs), wie Thalidomid und Lenalidomid. Zahlreiche klinische Studien prüfen aktuell den RANKL-(receptor activator of NF-κB ligand) neutralisierenden Antikörper Denosumab, Anti-Sclerostin (Antikörper gegen Sclerostin, den Wnt-Signalweg wiederherstellend und die Osteoklastenaktivität steigernd) oder Sotatercept (Inhibierung von Aktivin-A) in ihrem therapeutischen Potenzial. Der vorliegende Beitrag gibt einen Überblick über die Pathogenese, Diagnostik, Therapie und Prävention ossärer Komplikationen beim multiplen Myelom, welche in ähnlicher oder gleicher Weise auch für andere tumorbedingte Knochenmetastasen gelten.

Abstract

Multiple myeloma (MM) ranges second of all hematological malignancies and occurs most commonly in elderly patients. Almost all MM patients develop bone lesions in the course of their disease or have evidence of bone loss at initial diagnosis. Whole-body conventional radiography remains the gold standard in the diagnostic evaluation, albeit computed tomography (CT) and magnetic resonance imaging (MRI) are increasingly used as complementary techniques in the more sensitive detection of osteolytic processes. Bisphosphonates like zoledronate or pamidronate represent the cornerstone therapeutics in osteolytic disease, and are effective supportives to potent anti-myeloma therapies, including novel agents such as the proteasome inhibitor bortezomib or immunomodulatory drugs (IMIDs, e. g. thalidomide or lenalidomide). Several studies are ongoing to investigate the effects of alternative bone-seeking agents and their therapeutic potential for the management of myeloma bone disease, such as denosumab (RANKL-neutralizing antibody), anti-sclerostin (monoclonal antibody, generated against sclerostin) or sotatercept (potent activin-A inhibitor). This review summarizes the most prominent data on myeloma bone disease pathogenesis, the role of imaging techniques as well as therapy and prevention of lytic complications in myeloma which may similarly or equally be true for other bone metastases-inducing solid tumors.

Schlüsselwörter

Multiples Myelom - Ossäre Komplikationen - Therapie - Bisphosphonate

Keywords

multiple myeloma - osteolytic complications - therapy - bisphosphonates

• Literatur

• 1 Berenson J, Pflugmacher R, Jarzem P et al. Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial. Lancet Oncol 2011; 12: 225-235
• 2 Boonen S, Van Meirhaeghe J, Bastian L et al. Balloon kyphoplasty for the treatment of acute vertebral compression fractures: 2-year results from a randomized trial. J Bone Miner Res 2011; 26: 1627-1637
• 3 Delforge M, Terpos E, Richardson PG et al. Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan-prednisone vs. melphalan-prednisone in the phase III VISTA trial in multiple myeloma. Eur J Haematol 2011; 86: 372-384
• 4 Dimopoulos M, Terpos E, Comenzo RL et al. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma. Leukemia 2009; 23: 1545-1556
• 5 Durie BG, Katz M, Crowley J. Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 2005; 353: 99-102 und Diskusssion 199-202
• 6 Engelhardt M et al. Superiority of magnetic resonance imaging over conventional radiographs in multiple myeloma. Anticancer Res 2009; 29: 4745-4750
• 7 Engelhardt M, Udi J, Kleber M et al. European a Network: the 3rd Trialist Forum Consensus Statement from the European experts meeting on multiple myeloma. Leuk Lymphoma 2010; 51: 2006-2011
• 8 Fritzell P, Ohlin A, Borgstrom F. Cost-effectiveness of balloon kyphoplasty versus standard medical treatment in patients with osteoporotic vertebral compression fracture: a Swedish multicenter randomized controlled trial with 2-year follow-up. Spine (Phila Pa 1976) 2011; 36: 2243-2251
• 9 Gimsing P, Carlson K, Turesson I et al. Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic a Study Group): a double-blind, randomised controlled trial. Lancet Oncol 2010; 11: 973-982
• 10 Henry DH, Costa L, Goldwasser F et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 2011; 29: 1125-1132
• 11 Hussein MA et al. The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement. Leukemia 2008; 22: 1479-1484
• 12 McKiernan FE. Kyphoplasty and vertebroplasty: how good is the evidence?. Curr Rheumatol Rep 2007; 9: 57-65
• 13 Morgan G et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC a IX): a randomised controlled trial. Lancet 2010; 376: 1989-1999
• 14 Morgan GJ, Dimopoulos MA, Goldschmidt H, Moreau P. Personal communication, . Zenith Meeting München: 02.-05.02.2012
• 15 Moulopoulos LA, Dimopoulos MA, Alexanian R et al. Multiple myeloma: MR patterns of response to treatment. Radiology 1994; 193: 441-446
• 16 Raje N, Roodman GD. Advances in the biology and treatment of bone disease in multiple myeloma. Clin Cancer Res 2011; 17: 1278-1286
• 17 Rajkumar SV, Gahrton G, Bergsagel PL. Approach to the treatment of multiple myeloma: a clash of philosophies. Blood 2011; 118: 3205-3211
• 18 Richardson PG et al. The Medical Research Council Myeloma IX trial: the impact on treatment paradigms. Eur J Haematol 2012; 88: 1-7
• 19 Roodman GD. Pathogenesis of myeloma bone disease. Leukemia 2009; 23: 435-441
• 20 Terpos E et al. The effect of novel anti-myeloma agents on bone metabolism of patients with multiple myeloma. Leukemia 2007; 21: 1875-1884
• 21 Terpos E et al. Advances in imaging and the management of myeloma bone disease. J Clin Oncol 2011; 29: 1907-1915
• 22 Treister N, Woo SB. Images in clinical medicine. Bisphosphonate-associated osteonecrosis of the jaw. N Engl J Med 2006; 355: 2348
• 23 Wardlaw D et al. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled trial. Lancet 2009; 373: 1016-1024