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Perspectives
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nomenon: from 2000 until now, there have been 5- to 10- fold increases in the cost of new drugs.25 Price differences in Europe can, therefore, be substantially different from those in the USA (Table 1). In Germany, a benefit assess- ment of pharmaceuticals in accordance with the Act on the Reform of the Market for Medicinal Products (AMNOG) is limiting the cost of new pharmaceutical products. In the USA, a deflation of generic prices has been reported, due to an increasing number of competing companies entering the market. As clinicians and researchers we know that medical advances are needed, and developmental costs for new drugs have steadily increased with regulatory requirements. Goldstein reminds us of the financial burden associated with new cancer agents, which we offer to our patients with the aim to 'never harm but always aid': nevertheless, the judge- ment regarding bisphosphonate generics versus denosum- ab is biased and the comparison is cumbersome. His con- clusions that generic bisphosphonates have a novel coun- terpart and that the financial burden with denosumab is higher are, however, worth noting.24 Thus, the good news prevails that treatment options for the prevention of bone complications have increased with the introduction of denosumab, providing a new choice for patients and physicians. Once initiated, bisphosphonates or denosum- ab should be continued for at least 2 years, after which a suspension of bisphosphonate treatment may be consid- ered in very responsive patients, although this may be associated with skeletal risks, especially in those with prior skeletal complications. For patients in whom bis- phosphonates were stopped after 2 years, the drug should be resumed on a monthly basis if the MM recurs and/or new skeletal-related events occur, independently of the use of novel agent-based therapies.1–3
Acknowledgment
We are deeply indebted to esteemed experts of the Deutsche Studiengruppe Multiples Myelom, German Multiple Myeloma Study Group, European Myeloma Network Group and International Myeloma Working Group for their valuable dis- cussion.
References
1. Terpos E, Kleber M, Engelhardt M, et al. European Myeloma Network Guidelines for the management of multiple myeloma-relat- ed complications. Haematologica. 2015;100(10):1254-1266.
2. Terpos E, Christoulas D, Gavriatopoulou M. Biology and treatment of myeloma related bone disease. Metabolism. 2018;80:80-90.
3. Yee AJ, Raje NS. Denosumab for the treatment of bone disease in solid tumors and multiple myeloma. Future Oncol. 2018;14(3):195- 203.
4. Hillengass J, Fechtner K, Weber M-A, et al. Prognostic significance of focal lesions in whole-body magnetic resonance imaging in patients with asymptomatic multiple myeloma. J Clin Oncol. 2010;28(9):1606-1610.
5. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of mul- tiple myeloma. Lancet Oncol. 2014;15(12):e538-548.
6. Caers J, Fernández de Larrea C, Leleu X, et al. The changing land-
scape of smoldering multiple myeloma: a European perspective.
Oncologist. 2016;21(3):333-342.
7. Berenson JR, Lichtenstein A, Porter L, et al. Efficacy of pamidronate
in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med. 1996;334(8):488-493.
8. Berenson JR, Rosen LS, Howell A, et al. Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer. 2001;91(7):1191-1200.
9. Rosen LS, Gordon D, Kaminski M, et al. Zoledronic 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(5): 377-387.
10. RosenLS,GordonD,KaminskiM,etal.Long-termefficacyandsafe- ty of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multi- ple myeloma or breast carcinoma: a randomized, double-blind, mul- ticenter, comparative trial. Cancer. 2003;98(8):1735-1744.
11. 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.
12. Morgan GJ, Davies FE, Gregory WM, et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myelo- ma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010;376(9757):1989-1999.
13. 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 out- comes from a randomised controlled trial. Lancet Oncol. 2011;12(8):743-752.
14. 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.
15. Mhaskar R, Redzepovic J, Wheatley K, et al. Bisphosphonates in multiple myeloma: a network meta-analysis. Cochrane Database Syst Rev. 2012;(5):CD003188.
16. Raje N, Terpos E, Willenbacher W, et al. An international, ran- domised, double-blind study of denosumab compared to zoledronic acid in bone disease treatment of newly diagnosed multiple myelo- ma. Lancet Hematol. 2018;19(3):370-381.
17. GrazianiG,HergetG,IhorstG,etal.Timefromfirstsymptomonset to the final diagnosis of multiple myeloma - possible risks and future solutions: large retrospective and conformatory prospective “Deutsche Studiengruppe Multiples Myelom” (DSMM) analysis. Blood. 2017;130(Suppl 1):4710.
18. 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(5):372-384.
19. Mohty M, Malard F, Mohty B, Savani B, Moreau P, Terpos E. The effects of bortezomib on bone disease in patients with multiple myeloma. Cancer. 2014;120(5):618-623.
20. Engelhardt M, Terpos E, Kleber M, et al. European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma. Haematologica. 2014;99(2):232-242.
21. McIlroyG,MyttonJ,EvisonF,etal.Increasedfractureriskinplasma cell dyscrasias is associated with poorer overall survival. Br J Haematol. 2017;179(1):61-65.
22. Nash Smyth E, Conti I, Wooldridge JE, et al. Frequency of skeletal- related events and associated healthcare resource use and costs in US patients with multiple myeloma. J Med Econ. 2016;19(5):477-486.
23. Avilès A, Nambo M-J, Huerta-Guzmàn J, Cleto S, Neri N. Prolonged use of zoledronic acid (4 Years) did not improve outcome in multiple myeloma patients. Clin Lymphoma Myeloma Leuk. 2017;17(4):207- 210.
24. Goldstein D. Denosumab for bone lesions in multiple myeloma - what is its value? Haematologica. 2018(5):753-754.
25. Kantarjian H, Steensma D, Rius Sanjuan J, Elshaug A, Light D. High cancer drug prices in the United States: reasons and proposed solu- tions. J Oncol Pract. 2014;10(4):e208-211.
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