Blood Res.  2020 Jul;55(S1):S37-S42. 10.5045/br.2020.S007.

Frontline therapy for newly diagnosed patients with multiple myeloma

Affiliations
  • 1Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea
  • 2Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea

Abstract

Since the introduction of an alkylator to the treatment of multiple myeloma (MM), new effective agents have been developed, such as immunomodulatory drugs including thalidomide, lenalidomide, and pomalidomide; proteasome inhibitors including bortezomib, carfilzomib, and ixazomib; monoclonal antibodies including daratumumab and elotuzumab; and deacetylase inhibitors including panobinostat. Numerous regimens with these new agents have been developed and they have contributed in improving survival outcomes in MM patients. In addition, the recommended therapies for newly diagnosed MM change every year based on the results of clinical trials. This review will discusses the appropriate induction therapies based on recent clinical trials for patients with newly diagnosed MM.

Keyword

Multiple myeloma; Induction therapy; Prognosis

Cited by  1 articles

Comparative efficacy of VMP vs. Rd in newly diagnosed, autologous stem cell transplant‑ineligible multiple myeloma patients: a prematurely terminated randomized controlled study, CAREMM‑2002 study
Cheong Yoon Huh, Sung‑Soo Park, Jung Yeon Lee, Chang‑Ki Min
Blood Res. 2024;59:24.    doi: 10.1007/s44313-024-00025-7.


Reference

1. Kyle RA, Rajkumar SV. 2004; Multiple myeloma. N Engl J Med. 351:1860–73. DOI: 10.1056/NEJMra041875. PMID: 15509819.
Article
2. Siegel RL, Miller KD, Jemal A. 2015; Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. DOI: 10.3322/caac.21254. PMID: 25559415.
Article
3. Jung KW, Won YJ, Kong HJ, et al. 2015; Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2012. Cancer Res Treat. 47:127–41. DOI: 10.4143/crt.2015.060. PMID: 25761484. PMCID: PMC4398120.
Article
4. Lee JH, Lee DS, Lee JJ, et al. 2010; Multiple myeloma in Korea: past, present, and future perspectives. Experience of the Korean Multiple Myeloma Working Party. Int J Hematol. 92:52–7. DOI: 10.1007/s12185-010-0617-6. PMID: 20544403.
Article
5. Barlogie B, Smith L, Alexanian R. 1984; Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med. 310:1353–6. DOI: 10.1056/NEJM198405243102104. PMID: 6546971.
Article
6. Child JA, Morgan GJ, Davies FE, et al. 2003; High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 348:1875–83. DOI: 10.1056/NEJMoa022340. PMID: 12736280.
Article
7. Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Björkholm M. 2007; Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol. 25:1993–9. DOI: 10.1200/JCO.2006.09.0100. PMID: 17420512.
Article
8. Kumar SK, Rajkumar SV, Dispenzieri A, et al. 2008; Improved survival in multiple myeloma and the impact of novel therapies. Blood. 111:2516–20. DOI: 10.1182/blood-2007-10-116129. PMID: 17975015. PMCID: PMC2254544.
Article
9. Sonneveld P, Avet-Loiseau H, Lonial S, et al. 2016; Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 127:2955–62. DOI: 10.1182/blood-2016-01-631200. PMID: 27002115. PMCID: PMC4920674.
Article
10. Greipp PR, San Miguel J, Durie BG, et al. 2005; International staging system for multiple myeloma. J Clin Oncol. 23:3412–20. DOI: 10.1200/JCO.2005.04.242. PMID: 15809451.
11. Palumbo A, Avet-Loiseau H, Oliva S, et al. 2015; Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 33:2863–9. DOI: 10.1200/JCO.2015.61.2267. PMID: 26240224. PMCID: PMC4846284.
Article
12. Hanamura I, Stewart JP, Huang Y, et al. 2006; Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood. 108:1724–32. DOI: 10.1182/blood-2006-03-009910. PMID: 16705089. PMCID: PMC1895503.
Article
13. Boyd KD, Ross FM, Chiecchio L, et al. 2012; A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC myeloma IX trial. Leukemia. 26:349–55. DOI: 10.1038/leu.2011.204. PMID: 21836613. PMCID: PMC4545515.
Article
14. Walker BA, Mavrommatis K, Wardell CP, et al. 2019; A high-risk, double-hit, group of newly diagnosed myeloma identified by genomic analysis. Leukemia. 33:159–70. DOI: 10.1038/s41375-018-0196-8. PMID: 29967379. PMCID: PMC6326953.
Article
15. Decaux O, Lode L, Magrangeas F, et al. 2008; Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myelome. J Clin Oncol. 26:4798–805. DOI: 10.1200/JCO.2007.13.8545. PMID: 18591550.
16. Shaughnessy JD Jr, Zhan F, Burington BE, et al. 2007; A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 109:2276–84. DOI: 10.1182/blood-2006-07-038430. PMID: 17105813.
Article
17. Kuiper R, Broyl A, de Knegt Y, et al. 2012; A gene expression signature for high-risk multiple myeloma. Leukemia. 26:2406–13. DOI: 10.1038/leu.2012.127. PMID: 22722715.
Article
18. Moulopoulos LA, Dimopoulos MA, Kastritis E, et al. 2012; Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma: a single center experience on 228 patients. Am J Hematol. 87:861–4. DOI: 10.1002/ajh.23258. PMID: 22641455.
Article
19. Bartel TB, Haessler J, Brown TL, et al. 2009; F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma. Blood. 114:2068–76. DOI: 10.1182/blood-2009-03-213280. PMID: 19443657. PMCID: PMC2744568.
Article
20. Usmani SZ, Mitchell A, Waheed S, et al. 2013; Prognostic implications of serial 18-fluoro-deoxyglucose emission tomography in multiple myeloma treated with total therapy 3. Blood. 121:1819–23. DOI: 10.1182/blood-2012-08-451690. PMID: 23305732. PMCID: PMC3591801.
Article
21. Jung SH, Kwon SY, Min JJ, et al. 2019; (18)F-FDG PET/CT is useful for determining survival outcomes of patients with multiple myeloma classified as stage II and III with the Revised International Staging System. Eur J Nucl Med Mol Imaging. 46:107–15. DOI: 10.1007/s00259-018-4114-0. PMID: 30187105.
Article
22. Attal M, Harousseau JL, Stoppa AM, et al. 1996; A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med. 335:91–7. DOI: 10.1056/NEJM199607113350204. PMID: 8649495.
23. Koreth J, Cutler CS, Djulbegovic B, et al. 2007; High-dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: A systematic review and meta-analysis of randomized controlled trials. Biol Blood Marrow Transplant. 13:183–96. DOI: 10.1016/j.bbmt.2006.09.010. PMID: 17241924.
Article
24. Cavo M, Hájek R, Pantani L, et al. 2017; Autologous stem cell transplantation versus bortezomib-melphalan-prednisone for newly diagnosed multiple myeloma: second interim analysis of the phase 3 EMN02/HO95 Study. Blood (ASH Annual Meeting Abstracts). 130(Suppl 1):397.
25. Dhakal B, Szabo A, Chhabra S, et al. 2018; Autologous transplantation for newly diagnosed multiple myeloma in the era of novel agent induction: a systematic review and meta-analysis. JAMA Oncol. 4:343–50. DOI: 10.1001/jamaoncol.2017.4600. PMID: 29302684. PMCID: PMC5885822.
26. Kumar SK, Dingli D, Lacy MQ, et al. 2008; Autologous stem cell transplantation in patients of 70 years and older with multiple myeloma: Results from a matched pair analysis. Am J Hematol. 83:614–7. DOI: 10.1002/ajh.21191. PMID: 18429054.
Article
27. Bashir Q, Shah N, Parmar S, et al. 2012; Feasibility of autologous hematopoietic stem cell transplant in patients aged ≥70 years with multiple myeloma. Leuk Lymphoma. 53:118–22. DOI: 10.3109/10428194.2011.606942. PMID: 21780997.
Article
28. Cavo M, Tacchetti P, Patriarca F, et al. 2010; Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 376:2075–85. DOI: 10.1016/S0140-6736(10)61424-9. PMID: 21146205.
Article
29. Rosiñol L, Oriol A, Teruel AI, et al. 2012; Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 120:1589–96. DOI: 10.1182/blood-2012-02-408922. PMID: 22791289.
Article
30. Moreau P, Avet-Loiseau H, Facon T, et al. 2011; Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 118:5752–8. quiz 5982DOI: 10.1182/blood-2011-05-355081. PMID: 21849487.
Article
31. Moreau P, Hulin C, Macro M, et al. 2016; VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. Blood. 127:2569–74. DOI: 10.1182/blood-2016-01-693580. PMID: 27002117.
32. Cavo M, Pantani L, Pezzi A, et al. 2015; Bortezomib-thalidomide-dexamethasone (VTD) is superior to bortezomib-cyclophosphamide-dexamethasone (VCD) as induction therapy prior to autologous stem cell transplantation in multiple myeloma. Leukemia. 29:2429–31. DOI: 10.1038/leu.2015.274. PMID: 26442610.
Article
33. Rosiñol L, Oriol A, Rios R, et al. 2019; Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma. Blood. 134:1337–45. DOI: 10.1182/blood.2019000241. PMID: 31484647. PMCID: PMC6888142.
34. Gay F, Cerrato C, Petrucci MT, et al. 2019; Efficacy of carfilzomib lenalidomide dexamethasone (KRd) with or without transplantation in newly diagnosed myeloma according to risk status: Results from the FORTE trial. J Clin Oncol (ASCO Annual Meeting). 37(Suppl 15):abst 8002. DOI: 10.1200/JCO.2019.37.15_suppl.8002.
Article
35. Moreau P, Hulin C, Caillot D, et al. 2017; Ixazomib-lenalidomide-dexamethasone (IRd) combination before and after autologous stem cell transplantation (ASCT) followed by ixazomib maintenance is a safe and effective strategy in patients with newly diagnosed multiple myeloma (NDMM): A phase 2 study from the Intergroupe Francophone Du MyéLome (IFM). Blood (ASH Annual Meeting Abstracts). 130(Suppl 1):2021. DOI: 10.1182/blood.V128.22.674.674.
36. Kumar S, Flinn I, Richardson PG, et al. 2012; Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 119:4375–82. DOI: 10.1182/blood-2011-11-395749. PMID: 22422823.
Article
37. Moreau P, Attal M, Hulin C, et al. 2019; Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 394:29–38. DOI: 10.1016/S0140-6736(19)31240-1. PMID: 31171419.
38. San Miguel JF, Schlag R, Khuageva NK, et al. 2008; Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 359:906–17. DOI: 10.1056/NEJMoa0801479. PMID: 18753647.
39. Kim MK, Kim K, Min CK, et al. 2017; A prospective, open-label, multicenter, observational study to evaluate the efficacy and safety of bortezomib-melphalan-prednisone as initial treatment for autologous stem cell transplantation-ineligible patients with multiple myeloma. Oncotarget. 8:37605–18. DOI: 10.18632/oncotarget.16790. PMID: 28402945. PMCID: PMC5514934.
40. Facon T, Lee JH, Moreau P, et al. 2019; Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma. Blood. 133:1953–63. DOI: 10.1182/blood-2018-09-874396. PMID: 30819926.
Article
41. Facon T, Dimopoulos MA, Dispenzieri A, et al. 2018; Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. Blood. 131:301–10. DOI: 10.1182/blood-2017-07-795047. PMID: 29150421. PMCID: PMC5774211.
Article
42. Durie BGM, Hoering A, Abidi MH, et al. 2017; Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 389:519–27. DOI: 10.1016/S0140-6736(16)31594-X. PMID: 28017406. PMCID: PMC5546834.
Article
43. O'Donnell EK, Laubach JP, Yee AJ, et al. 2018; A phase 2 study of modified lenalidomide, bortezomib and dexamethasone in transplant-ineligible multiple myeloma. Br J Haematol. 182:222–30. DOI: 10.1111/bjh.15261. PMID: 29740809. PMCID: PMC6074026.
44. Facon T, Kumar S, Plesner T, et al. 2019; Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 380:2104–15. DOI: 10.1056/NEJMoa1817249. PMID: 31141632.
Article
45. Mateos MV, Dimopoulos MA, Cavo M, et al. 2018; Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 378:518–28. DOI: 10.1056/NEJMoa1714678. PMID: 29231133.
Full Text Links
  • BR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr