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Changes in survival rate of multiple myeloma after the introduction of bortezomib: a single institutional experience over 20 years

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Abstract

The data of factors on the changes in survival before and after the introduction of bortezomib in unselected multiple myeloma (MM) patients is scarce in Asian population. We analyzed the clinical features and treatment outcomes of 270 consecutive MM patients admitted to our hospital between January 1995 and August 2014. The patients were divided into two groups, 1995–2005 (n = 106) and 2006–2014 (n = 164), based on bortezomib availability. There were no differences in baseline characteristics between the groups, except age and percentage of patients receiving autologous stem cell transplantation (auto-SCT). The proportion of patients obtaining ≥very good partial response (VGPR) was higher in the recent cohort, which was translated as better overall survival in both younger and older patients (36.1 vs. 79.8 months, P = 0.024, and 40.0 vs. 110.7 months, respectively). Patients receiving bortezomib early after diagnosis showed significantly better survival. However, there was no difference in survival between patients obtaining ≥VGPR in the two groups. On multivariate analysis, age ≥75 and lactate dehydrogenase (LDH) >normal were associated with shorter survival, while early bortezomib use and auto-SCT were associated with longer survival. On Cox regression analysis, International Staging System (ISS) stage III, LDH, and treatment response <VGPR in the previous cohort and ISS stage III, creatinine ≥2.0 mg/dL, and treatment response <VGPR in the recent cohort were associated with poorer survival. Our observations indicated marked improvement of survival in MM patients diagnosed from 2006 to 2014 mainly due to the availability of bortezomib in Japan.

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References

  1. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T et al (2005) Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352(24):2487–2498. doi:10.1056/NEJMoa043445, e-pub ahead of print 2005/06/17

    Article  PubMed  CAS  Google Scholar 

  2. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M et al (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 359(9):906–917. doi:10.1056/NEJMoa0801479

    Article  PubMed  CAS  Google Scholar 

  3. Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK et al (2008) Improved survival in multiple myeloma and the impact of novel therapies. Blood 111(5):2516–2520. doi:10.1182/blood-2007-10-116129, e-pub ahead of print 2007/11/03

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Turesson I, Velez R, Kristinsson SY, Landgren O (2010) Patterns of improved survival in patients with multiple myeloma in the twenty-first century: a population-based study. J Clin Oncol 28(5):830–834. doi:10.1200/JCO.2009.25.4177, e-pub ahead of print 2009/12/30

    Article  PubMed  PubMed Central  Google Scholar 

  5. Avet-Loiseau H, Hulin C, Campion L, Rodon P, Marit G, Attal M et al (2013) Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the intergroupe francophone du myelome experience. J Clin Oncol 31(22):2806–2809. doi:10.1200/JCO.2012.46.2598, e-pub ahead of print 2013/06/26

    Article  PubMed  PubMed Central  Google Scholar 

  6. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Blade J et al (2005) International staging system for multiple myeloma. J Clin Oncol 23(15):3412–3420. doi:10.1200/JCO.2005.04.242, e-pub ahead of print 2005/04/06

    Article  PubMed  Google Scholar 

  7. Kastritis E, Zervas K, Symeonidis A, Terpos E, Delimbassi S, Anagnostopoulos N et al (2009) Improved survival of patients with multiple myeloma after the introduction of novel agents and the applicability of the International Staging System (ISS): an analysis of the Greek Myeloma Study Group (GMSG). Leukemia 23(6):1152–1157. doi:10.1038/leu.2008.402

    Article  PubMed  CAS  Google Scholar 

  8. Iriuchishima H, Saitoh T, Handa H, Isoda A, Matsumoto M, Sawamura M et al. A new staging system to predict prognosis of patients with multiple myeloma in an era of novel therapeutic agents. European J Haematology 2014. e-pub ahead of print 2014/07/02; doi: 10.1111/ejh.12407

  9. Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Bjorkholm 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(15):1993–1999. doi:10.1200/JCO.2006.09.0100

    Article  PubMed  Google Scholar 

  10. Dimopoulos MA, Kastritis E, Delimpasi S, Katodritou E, Hatzimichael E, Kyrtsonis MC et al (2012) Multiple myeloma in octogenarians: clinical features and outcome in the novel agent era. Eur J Haematol 89(1):10–15. doi:10.1111/j.1600-0609.2012.01784.x, e-pub ahead of print 2012/04/04

    Article  PubMed  CAS  Google Scholar 

  11. Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K et al (2006) International uniform response criteria for multiple myeloma. Leukemia 20(9):1467–1473. doi:10.1038/sj.leu.2404284, e-pub ahead of print 2006/07/21

    Article  PubMed  CAS  Google Scholar 

  12. Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G et al (1998) Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 102(5):1115–1123, e-pub ahead of print 1998/09/30

    Article  PubMed  CAS  Google Scholar 

  13. Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48(3):452–458. doi:10.1038/bmt.2012.244

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Wada M, Mizoguchi H, Kuriya SI, Taguchi H, Kawamura T, Maekawa I et al (2000) Induction therapy consisting of alternating cycles of ranimustine, vincristine, melphalan, dexamethasone and interferon alpha (ROAD-IN) and a randomized comparison of interferon alpha maintenance in multiple myeloma: a co-operative study in Japan. Br J Haematol 109(4):805–814, e-pub ahead of print 2000/08/06

    Article  PubMed  CAS  Google Scholar 

  15. Barlogie B, Smith L, Alexanian R (1984) Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med 310(21):1353–1356. doi:10.1056/NEJM198405243102104

    Article  PubMed  CAS  Google Scholar 

  16. Imamura Y, Takagi T, Yawata Y, Nishinarita S, Kosaka M, Mikuni C et al (1994) Combination chemotherapy with MCNU, vindesine, melphalan, and prednisolone (MCNU-VMP therapy) in induction therapy for multiple myeloma. Japan Myeloma Study Group. Int J Hematol 59(2):113–123, e-pub ahead of print 1994/02/01

    PubMed  CAS  Google Scholar 

  17. Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR et al (2002) Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 20(21):4319–4323

    Article  PubMed  CAS  Google Scholar 

  18. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D et al (2003) A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348(26):2609–2617. doi:10.1056/NEJMoa030288

    Article  PubMed  CAS  Google Scholar 

  19. Pineda-Roman M, Zangari M, van Rhee F, Anaissie E, Szymonifka J, Hoering A et al (2008) VTD combination therapy with bortezomib-thalidomide-dexamethasone is highly effective in advanced and refractory multiple myeloma. Leukemia 22(7):1419–1427. doi:10.1038/leu.2008.99

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Mateos MV, Hernandez JM, Hernandez MT, Gutierrez NC, Palomera L, Fuertes M et al (2006) Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood 108(7):2165–2172, 10.1182/blood-2006-04-019778

    Article  PubMed  CAS  Google Scholar 

  21. Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B et al (2007) Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet 370(9594):1209–1218. doi:10.1016/S0140-6736(07)61537-2, e-pub ahead of print 2007/10/09

    Article  PubMed  CAS  Google Scholar 

  22. Ludwig H, Adam Z, Hajek R, Greil R, Tothova E, Keil F et al (2010) Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: results of a phase II study. J Clin Oncol 28(30):4635–4641. doi:10.1200/JCO.2010.28.1238, e-pub ahead of print 2010/09/09

    Article  PubMed  CAS  Google Scholar 

  23. Brenner H, Gondos A, Pulte D (2008) Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood 111(5):2521–2526. doi:10.1182/blood-2007-08-104984

    Article  PubMed  CAS  Google Scholar 

  24. Warren JL, Harlan LC, Stevens J, Little RF, Abel GA (2013) Multiple myeloma treatment transformed: a population-based study of changes in initial management approaches in the United States. J Clin Oncol 31(16):1984–1989. doi:10.1200/JCO.2012.46.3323

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Palumbo A, Bringhen S, Ludwig H, Dimopoulos MA, Blade J, Mateos MV et al (2011) Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood 118(17):4519–4529. doi:10.1182/blood-2011-06-358812, e-pub ahead of print 2011/08/16

    Article  PubMed  CAS  Google Scholar 

  26. Merz M, Neben K, Raab MS, Sauer S, Egerer G, Hundemer M et al (2014) Autologous stem cell transplantation for elderly patients with newly diagnosed multiple myeloma in the era of novel agents. Ann Oncol 25(1):189–195. doi:10.1093/annonc/mdt509

    Article  PubMed  CAS  Google Scholar 

  27. Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S et al (2014) Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia 28(5):1122–1128. doi:10.1038/leu.2013.313

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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Conflict of interest

The authors have no conflicts of interest.

Authorship statement

MF and KM designed the study and wrote the manuscript. MF, KS, KF, YS, MF, HS, and MT provided clinical care and performed laboratory examinations. MF and KM collected and analyzed data and performed statistical analysis.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Kameda Medical Center, 929 Higashi-chou, Kamogawa-shi, Chiba, 296-8602, Japan

    Manabu Fujisawa, Yasuhito Suehara, Kota Fukumoto, Masami Takeuchi & Kosei Matsue

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  1. Manabu Fujisawa
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  2. Yasuhito Suehara
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  3. Kota Fukumoto
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  4. Masami Takeuchi
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  5. Kosei Matsue
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Correspondence to Kosei Matsue.

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Fujisawa, M., Suehara, Y., Fukumoto, K. et al. Changes in survival rate of multiple myeloma after the introduction of bortezomib: a single institutional experience over 20 years. Ann Hematol 95, 63–72 (2016). https://doi.org/10.1007/s00277-015-2522-9

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  • DOI: https://doi.org/10.1007/s00277-015-2522-9

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