Denosumab and bisphosphonates in multiple myeloma in 2019
Authors:
Z. Král; Z. Adam; M. Krejčí; L. Pour; V. Sandecká; M. Štork
Authors‘ workplace:
Interní hematologická a onkologická klinika LF MU a FN Brno
Published in:
Transfuze Hematol. dnes,25, 2019, No. 4, p. 320-329.
Category:
Review/Educational Papers
Overview
More than 80% of patients with multiple myeloma display evidence of myeloma bone disease (MBD) characterised by the formation of osteolytic lesions throughout the axial and appendicular skeleton. MBD significantly increases the risk of skeletal-related events such as pathological fractures, spinal cord compression and hypercalcaemia. MBD is the result of MM plasma cell-mediated activation of osteoclast activity and suppression of osteoblast activity. The activity of osteoclasts can be suppressed using bisphosphonates (BP) or denosumab. Although generally safe, frequent high doses of BP are associated with adverse events such as renal toxicity and osteonecrosis of the jaw and atypical fractures. As such, optimal duration and dosing of BP therapy is required in order to minimise BP-associated adverse events. The following review provides currently available evidence for the adoption of a tailored approach when using BP for the management of MBD.
Keywords:
bisphosphonates – medication related osteonecrosis of the jaw – atypical fractures – Multiple myeloma
Sources
1. Russell RG. Bisphosphonates: the first 40 years. Bone 2011;49(1):2–19.
2. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61(9):1115–1117.
3. Ruggiero SL, Mehrota B. Osteonecrosis of the jaws associated with the use of bisphophonates; a review of 63 cases. J Oral Maxillofac Surg 2004;62:527–534.
4. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonates--induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention and treatment. J Oral Maxillofac Surg 2005;63:1567–1575.
5. Ferlito S, Liardo C, Puzzo S. Bisphosponates and dental implants: a case report and a brief review of literature. Minerva Stomatol 2011;60(1–2):75–81.
6. Montoya-Carralero JM, Parra-Mino P, Ramírez-Fernández P, et al. Dental implants in patients treated with oral bisphosphonates: a bibliographic review. Med Oral Patol Oral Cir Bucal 2010;15(1):e65–e69.
7. Favia G, Piattelli A, Sportelli P, Capodiferro S, Iezzi G. Osteonecrosis of the posterior mandible after implant insertion: a clinical and histological case report. Clin Implant Dent Relat Res 2011;13(1):58–63.
8. Treglerová J, Zelinka J, Adam Z, et al. Osteonekróza čelisti, atypické fraktury kostí a další méně časté nežádoucí účinky bisfosfonátů. Transfuze Hematol dnes; v tisku.
9. Lenart BA, Lorich DG, Lane JM. Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med 2008;358(12):1304–1306.
10. Puhaindran ME, Farooki A, Steensma MR, et al. Atypical subtrochanteric femoral fractures in patients with skeletal malignant involvement treated with intravenous bisphosphonates. J Bone Joint Surg Am 2011;93(13):1235–1242.
11. Delmas PD, Charhon S, Chapuy E, et al. Long term effects of dichloromethylene diphosphate (C12MDP) on skeletal lesions in multiple myeloma. Metabol Bone Dis Rel Res 1982;4:163–168.
12. Lahtinen R, Laakso M, Palva I, et al. Randomised, placebo controlled multicentre trial of clodronate in multiple myeloma. Finnish Leukemia Group. Lancer 1992;340:1049–1052.
13. Closkey EV, MacLennan IC, Drayson MT, et al. A randomized trial of the effect of clodronate on skeletal morbitidy in multiple myeloma. MRC Working Party on Leukemia in Aduls. Brit J Haematol 1998;100:317–325.
14. Berenson JR, Lichtenstein A, Porter L, et al. Efficacy of pamidronate in reducing skeletal events in patientes with advanced multiple myeloma. N Engl J Med 1996;334:488–493.
15. Berenson JR, Lichtenstein A, Porter L, et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol 1998;16(2):593–602.
16. Rosen LS, Gordon D, Tchekmedyian NS, et al. Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial – the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol 2003;15:31500–3157.
17. Adam Z, Ševčík P, Vorlíček J, et al. Kostní nádorová choroba. Praha, Grada 2005, 296s.
18. Menssen HD, Sakalová A, Fontana A, et al. Effects of long-term intravenous ibandronate therapy on skeletal-related events, survival, and bone resorption markers in patients with advanced multiple myeloma. J Clin Oncol 2002;20(9):2353–2359.
19. Body JJ, Diel IJ, Lichinitser MR, et al. Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Ann Oncol 2003; 14:1399–1405.
20. Barrett-Lee P, Casbard A, Abraham J, et al. Oral ibandronic acid versus intravenous zoledronic acid in treatment of bone metastases from breast cancer: a randomised, open label, non-inferiority phase 3 trial. Lancet Oncol 2014;15(1):114–122.
21. Body JJ, Lichinitser M, Tjulandin S, et al. Oral ibandronate is as active as intravenous zoledronic acid for reducing bone turnover markers in women with breast cancer and bone metastases. Ann Oncol 2017;18(7):1165–1171.
22. Pecherstorfer M, Rivkin S, Body J, et al. Long-term safety of intravenous ibandronic acid for up to 4 years in metastatic breast cancer: an open-label trial. Clin Drug Investig 2006; 26(6):315–322.
23. Knauf W, Berger R, Kropff M, et al. Compare – result of a randomised study to assess the renal safety nad efficacy of ibandronate and zoledronate in multiple myeloma patients. Onkologie 2010;33(Suppl 6):246 (abstr. 824).
24. Geng CJ, Liang Q, Zhong JH, et al. Ibandronate to treat skeletal-related events and bone pain in metastatic bone disease or multiple myeloma: a meta-analysis of randomised clinical trials. BMJ Open 2015;5(6):e007258.
25. Chen F, Pu F. Safety of denosumab versus zoledronic acid in patients with bone metastases: a meta-analysis of randomized controlled trials. Oncol Res Treat 2016;39(7–8): 453–459.
26. Raje N, Terpos E, Willenbacher W, Krejčí M, et al. An international randomised trial comparing denosumab with zoledronic acid for the treatment of bone disease in patients with newly diagnosed multiple myelom. 16th International Myeloma Workshop March 1–4. 2017 New Delhi, abstrakt OP-046 e39.
27. Raje N, Terpos E, Willenbacher W, et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol 2018;19(3):370–381.
28. Raje N, Vadhan-Raj S, Willenbacher W, et al. Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial. Blood Cancer J 2016;6:e378. doi: 10.1038/bcj.2015.96.
29. Goldstein DA. Denosumab for bone lesions in multiple myeloma – what is its value? Haematologica 2018;103(5):753–754.
30. Raje N, Roodman GD, Willenbacher W, et al. A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in the United States of America. J Med Econ 2018;21(5):525–536.
31. Yee AJ, Raje NS. Denosumab for the treatment of bone disease in solid tumors and multiple myeloma. Future Oncol 2018;14(3):195–203.
32. Gavriatopoulou M, Dimopoulos MA, Kastritis E, et al. Emerging treatment approaches for myeloma-related bone disease. Expert Rev Hematol 2017; 10(3): 217–228.
33. Vallet S, Filzmoser JM, Pecherstorfer M, et al. Update on pathogenesis and novel treatment strategies. Pharmaceutics 2018;10(4) pii:E202. doi: 10.3390/pharmaceutics10040202.
34. Dimopoulos MA, Kastritis E. Denosumab for myeloma bone disease: ready for prime time? Lancet Oncol 2018;19(3):277–278.
35. Marlow CF, Sharma S, Babar F, et al. Severe hypocalcemia and hypomagnesemia with denosumab in advanced chronic kidney disease: case report and literature review. Case Rep Oncol Med 2018;2018:2059364. doi: 10.1155/2018/2059364.
36. Terpos E, Christoulas D, Gavriatopoulou M. Biology and treatment of myeloma related bone disease. Metabolism 2018;80:80–90.
37. Ross JR, Saunders Y, Edmonds PM, et al. A systematic review of the role of bisphosphonates in metastatic disease. Health Technol Assess 2004;8(4):1–176.
38. Ross JR, Saunders Y, Edmonds PM, et al. Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer. BMJ 2003;327(7413):469.
39. Rosen LS, Gordon D, Kaminski M, et al. Zolendronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma. A phase III double blind comparative trial. Cancer J 2001;7:377–387.
40. 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 Myeloma Study Group): a double-blind, randomised controlled trial. Lancet Oncol 2010;11(10):973–982.
41. Morgan GJ, Davies FE, Gregory WM, et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet 2010;376(9757):1989–1999.
42. Morgan GJ, Child JA, Gregory WM, et al. Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial. Lancet Oncol 2011; 12(8): 743–752.
43. Morgan GJ, Davies FE, Gregory WM, et al. Effects of induction and maintenance plus long-term bisphosphonates on bone disease in patients with multiple myeloma: the Medical Research Council Myeloma IX Trial. Blood 2012;119(23):5374–5383.
44. Mhaskar R, Redzepovic J, Wheatley K, et al. Bisphosphonates in multiple myeloma: a network meta-analysis. Cochrane Database Syst Rev 2012;(5):CD003188. doi: 10.1002/14651858.CD003188.
45. Mhaskar R, Kumar A, Miladinovic B, et al. Bisphosphonates in multiple myeloma: an updated network meta-analysis. Cochrane Database Syst Rev 2017;12:CD003188. doi: 10.1002/14651858.CD003188.
46. Fung P, Bedogni G, Bedogni A, et al. Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study. Oral Dis 2016. doi: 10.1111/odi.12632.
47. Terpos E, Morgan G, Dimopoulos MA, et al. International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease. J Clin Oncol 2013;31(18):2347–2357.
48. Snowden JA, Ahmedzai SH, Ashcroft J, et al. Guidelines for supportive care in multiple myeloma 2011. Br J Haematol 2011;154(1):76–103.
49. Terpos E, Sezer O, Croucher PI, et al. The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network. Ann Oncol 2009;20(8):1303–1317.
50. Kyle RA, Yee GC, Somerfield MR, et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 2007;25(17):2464–2472.
51. García-Sanz R, Oriol A, Moreno MJ, et al for Spanish Myeloma Group (GEM/PETHEMA). Zoledronic acid as compared with observation in multiple myeloma patients at biochemical relapse: results of the randomized AZABACHE Spanish trial. Haematologica 2015;100(9):1207–1213.
52. Lee OL, Horvath N, Lee C, et al. Bisphosphonate guidelines for treatment and prevention of myeloma bone disease. Internal Medicine J 2017;47:938–951.
53. McGrath LJ, Hernandez RK, Overman R, et al. Initiation and interruption in intravenous bisphosphonate therapy among patients with multiple myeloma in the United States. Cancer Med 2019;8(1):374–382.
54. Leng S, Chen Y, Tsai WY, et al. Use of bisphosphonates in elderly patients with newly diagnosed multiple myeloma. J Natl Compr Canc Netw 2019;17(1):22–28.
55. Witzig TE, Laumann KM, Lacy MQ, et al. A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma. Leukemia 2013;27(1):220–225.
56. D‘Arena G, Gobbi PG, Broglia C, et al. Pamidronate versus observation in asymptomatic myeloma: final results with long-term follow-up of a randomized study. Leuk Lymphoma 2011;52(5):771–775.
57. Musto P, Petrucci MT, Bringhen S, et al. A multicenter, randomized clinical trial comparing zoledronic acid versus observation in patients with asymptomatic myeloma. Cancer 2008;113(7):1588–1595.
58. Henrich DM, Hoffmann M, Uppenkamp M, et al. Tolerability of dose escalation of ibandronate in patients with multiple myeloma and end-stage renal disease: a case series. Onkologie 2009;32(8–9):482–486.
59. Bergner R, Henrich DM, Hoffmann M, et al. Renal safety and pharmacokinetics of ibandronate in multiple myeloma patients with or with-out impaired renal function. J Clin Pharmacol 2007;47(8):942–950.
60. Bergner R, Henrich DM, Hoffmann M, etl al. Therapy of hypercalcemia with ibandronate in case of acute renal failure. Internist (Berl) 2006;47(3):293–296.
61. Diel IJ, Weide R, Köppler H, et al. Risk of renal impairment after treatment with ibandronate versus zoledronic acid: a retrospective medical records review. Support Care Cancer 2009;17(6):719–725.
62. Henrich D, Hoffmann M, Uppenkamp M, et al. Ibandronate for the treatment of hypercalcemia or nephrocalcinosis in patients with multiple myeloma and acute renal failure: Case reports. Acta Haematol 2006;116(3):165–172.
63. Jackson GH. Renal safety of ibandronate. Oncologist 2005;10(Suppl 1):14–18.
64. Maisnar V, Pour L, Krejčí M, et al. Doporučení vypracované Českou myelomovou skupinou, Myelomovou sekcí České hematologické společnosti a Slovenskou Myelomovou Spoločností pro diagnostiku a léčbu mnohočetného myelomuu mnohočetného myelomu. Transfuze Hematol dnes 2018;24(Supl 1):1–157.
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