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Survival differences in multiple myeloma in Latin America and Asia: a comparison involving 3664 patients from regional registries

  • Vania T. M. HungriaEmail author
  • Jae Hoon Lee
  • Angelo Maiolino
  • Edvan de Queiroz Crusoe
  • Gracia Martinez
  • Rosane Bittencourt
  • Gislaine Oliveira Duarte
  • Dorotea Beatriz Fantl
  • Juan Ramon Navarro
  • Guillermo Conte
  • David Gomez-Almaguer
  • Guillermo J. Ruiz-Argüelles
  • Kihyun Kim
  • Kazuyuki Shimizu
  • Wenming Chen
  • Shang-YI Huang
  • Wee-Joo Chng
  • Chor Sang Chim
  • Weerasak Nawarawong
  • Brian Durie
Original Article
  • 27 Downloads

Abstract

In previous observational studies, we have separately characterized patients with multiple myeloma (MM) both from Latin America (LA) and from Asia. Here, we analyze these two datasets jointly, in order to assess the overall survival (OS) in these two world regions. Data were available from 3664 patients (1968 from LA and 1696 from Asia); all of whom diagnosed between 1998 and 2007. Approximately, 26% of patients in both world regions underwent transplantation. OS (from diagnosis of MM) was explored with Kaplan–Meier analyses and Cox proportional hazards models. Patients from LA were significantly younger and had hypercalcemia more often than Asian patients, who in turn had higher proportions of anemia and International Staging System (ISS) stage III disease. The median OS was 56 months in LA, and 47 months in Asia (hazard ratio [HR] = 0.83; 95% confidence interval [CI], 0.76 to 0.91; P < 0.001). In multivariable analysis, age, ISS stage III, anemia, hypercalcemia, and world region remained significantly associated with OS (P < 0.001 for all covariates). These results were largely driven by patients not undergoing transplantation, as no difference in OS emerged between the two world regions in univariable or multivariable analysis for transplanted patients. Despite adverse prognostic features differentially favoring each region, and adjusting for such differences, we found an OS advantage for patients from LA, in comparison with contemporaneous patients from Asia. Whether this is due to different biological features, differences in access to novel agents (especially thalidomide in earlier periods of the study), unmeasured confounders, or the play of chance, remain unknown.

Keywords

Multiple myeloma Survival analysis Latin America and Asia 

Notes

Compliance with ethical standards

The protocol for each study was approved by the competent local authorities and institutional review boards, and written informed consent was obtained from all patients.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

277_2019_3602_MOESM1_ESM.docx (53 kb)
ESM 1 (DOCX 52 kb)

References

  1. 1.
    Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA (2008) Improved survival in multiple myeloma and the impact of novel therapies. Blood 111:2516–2520CrossRefGoogle Scholar
  2. 2.
    Moreau P, Attal M, Facon T (2015) Frontline therapy of multiple myeloma. Blood 125:3076–3084CrossRefGoogle Scholar
  3. 3.
    Palumbo A, Anderson K (2011) Multiple myeloma. N Engl J Med 364:1046–1060CrossRefGoogle Scholar
  4. 4.
    Myeloma Trialists’ Collaborative Group (1998) Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. Myeloma Trialists' Collaborative Group. J Clin Oncol 16:3832–3842Google Scholar
  5. 5.
    Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis N, Banos A, Tiab M, Delforge M, Cavenagh J, Geraldes C, Lee JJ, Chen C, Oriol A, de la Rubia J, Qiu L, White DJ, Binder D, Anderson K, Fermand JP, Moreau P, Attal M, Knight R, Chen G, van Oostendorp J, Jacques C, Ervin-Haynes A, Avet-Loiseau H, Hulin C, Facon T, FIRST Trial Team (2014) Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med 371:906–917CrossRefGoogle Scholar
  6. 6.
    Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jędrzejczak W, Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M, Kloczko J, Bladé J, Beksac M, Spicka I, Plesner T, Radke J, Langer C, Ben Yehuda D, Corso A, Herbein L, Yu Z, Mei J, Jacques C, Dimopoulos MA, MM-015 Investigators (2012) Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 366:1759–1769CrossRefGoogle Scholar
  7. 7.
    Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, Stoppa AM, Hulin C, Benboubker L, Garderet L, Decaux O, Leyvraz S, Vekemans MC, Voillat L, Michallet M, Pegourie B, Dumontet C, Roussel M, Leleu X, Mathiot C, Payen C, Avet-Loiseau H, Harousseau JL, IFM Investigators (2012) Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 366:1782–1791CrossRefGoogle Scholar
  8. 8.
    Palumbo A, Cavallo F, Gay F, di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omedé P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M (2014) Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med 371:895–905CrossRefGoogle Scholar
  9. 9.
    Hungria VT, Crusoé EQ, Maiolino A, et al (2016) Phase 3 trial of three thalidomide-containing regimens in patients with newly diagnosed multiple myeloma not transplant-eligible. Ann Hematol 95:271–278Google Scholar
  10. 10.
    Agência Nacional de Saúde Suplementar. Dados e Indicadores do Setor. Beneficiários de planos privados de saúde. Available at http://www.ans.gov.br/perfil-do-setor/dados-e-indicadores-do-setor. Accessed 27 May 2018
  11. 11.
    Tan D, Chng WJ, Chou T, Nawarawong W, Hwang SY, Chim CS, Chen W, Durie BGM, Lee JH (2013) Management of multiple myeloma in Asia: resource-stratified guidelines. Lancet Oncol 14:e571–e581CrossRefGoogle Scholar
  12. 12.
    Tarin-Arzaga L, Arredondo-Campos D, Martinez-Pacheco V et al (2018) Impact of the affordability of novel agents in patients with multiple myeloma: real-world data of current clinical practice in Mexico. Cancer 124:1946–1953CrossRefGoogle Scholar
  13. 13.
    De Angelis R, Minicozzi P, Sant M et al (2015) Survival variations by country and age for lymphoid and myeloid malignancies in Europe 2000-2007: results of EUROCARE-5 population-based study. Eur J Cancer 51:2254–2268CrossRefGoogle Scholar
  14. 14.
    Hungria VT, Maiolino A, Martinez G et al (2008) Confirmation of the utility of the International Staging System and identification of a unique pattern of disease in Brazilian patients with multiple myeloma. Haematologica 93:791–792CrossRefGoogle Scholar
  15. 15.
    Hungria VT, Maiolino A, Martinez G et al (2017) Observational study of multiple myeloma in Latin America. Ann Hematol 96:65–72CrossRefGoogle Scholar
  16. 16.
    Kim K, Lee JH, Kim JS, Min CK, Yoon SS, Shimizu K, Chou T, Kosugi H, Suzuki K, Chen W, Hou J, Lu J, Huang XJ, Huang SY, Chng WJ, Tan D, Teoh G, Chim CS, Nawarawong W, Siritanaratkul N, Durie BG (2014) Clinical profiles of multiple myeloma in Asia-an Asian myeloma network study. Am J Hematol 89:751–756CrossRefGoogle Scholar
  17. 17.
    Greipp PR, San Miguel J, Durie BG et al (2005) International staging system for multiple myeloma. J Clin Oncol 23:3412–3420CrossRefGoogle Scholar
  18. 18.
    Schemper M, Smith TL (1996) A note on quantifying follow-up in studies of failure time. Control Clin Trials 17:343–346CrossRefGoogle Scholar
  19. 19.
    Richardson PG, San Miguel JF, Moreau P, Hajek R, Dimopoulos MA, Laubach JP, Palumbo A, Luptakova K, Romanus D, Skacel T, Kumar SK, Anderson KC (2018) Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting. Blood Cancer J 8:109CrossRefGoogle Scholar
  20. 20.
    Lee W, Nelson R, Mailey B, Duldulao MP, Garcia-Aguilar J, Kim J (2012) Socioeconomic factors impact colon cancer outcomes in diverse patient populations. J Gastrointest Surg 16:692–704CrossRefGoogle Scholar
  21. 21.
    Zell JA, Rhee JM, Ziogas A, Lipkin SM, Anton-Culver H (2007) Race, socioeconomic status, treatment, and survival time among pancreatic cancer cases in California. Cancer Epidemiol Biomark Prev 16:546–552CrossRefGoogle Scholar
  22. 22.
    Wang M, Burau KD, Fang S, Wang H, Du XL (2008) Ethnic variations in diagnosis, treatment, socioeconomic status, and survival in a large population-based cohort of elderly patients with non-Hodgkin lymphoma. Cancer 113:3231–3241CrossRefGoogle Scholar
  23. 23.
    Fiala MA, Finney JD, Liu J, Stockerl-Goldstein KE, Tomasson MH, Vij R, Wildes TM (2015) Socioeconomic status is independently associated with overall survival in patients with multiple myeloma. Leuk Lymphoma 56:2643–2649CrossRefGoogle Scholar
  24. 24.
    Hong S, Rybicki L, Abounader D, Bolwell BJ, Dean R, Gerds AT, Hamilton BK, Hill BT, Jagadeesh D, Kalaycio M, Liu HD, Pohlman B, Sobecks R, Majhail NS (2016) Association of socioeconomic status with outcomes of autologous hematopoietic cell transplantation for multiple myeloma. Biol Blood Marrow Transplant 22:1141–1144CrossRefGoogle Scholar
  25. 25.
    Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, Kapoor P, Dingli D, Hayman SR, Leung N, Lust J, McCurdy A, Russell SJ, Zeldenrust SR, Kyle RA, Rajkumar SV (2014) Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia 28:1122–1128CrossRefGoogle Scholar
  26. 26.
    US Department of Health and Human Services. National Institutes of Health. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Myeloma. Available at https://seer.cancer.gov/statfacts/html/mulmy.html (Accessed 28 December 2018)

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Vania T. M. Hungria
    • 1
    Email author
  • Jae Hoon Lee
    • 2
  • Angelo Maiolino
    • 3
  • Edvan de Queiroz Crusoe
    • 4
  • Gracia Martinez
    • 5
  • Rosane Bittencourt
    • 6
  • Gislaine Oliveira Duarte
    • 7
  • Dorotea Beatriz Fantl
    • 8
  • Juan Ramon Navarro
    • 9
  • Guillermo Conte
    • 10
  • David Gomez-Almaguer
    • 11
  • Guillermo J. Ruiz-Argüelles
    • 12
  • Kihyun Kim
    • 13
  • Kazuyuki Shimizu
    • 14
  • Wenming Chen
    • 15
  • Shang-YI Huang
    • 16
  • Wee-Joo Chng
    • 17
  • Chor Sang Chim
    • 18
  • Weerasak Nawarawong
    • 19
  • Brian Durie
    • 20
  1. 1.Santa Casa Medical SchoolSao PauloBrazil
  2. 2.Hematology-Oncology, Division of Hematology/OncologyGachon University Gil Medical CenterIncheonRepublic of South Korea
  3. 3.Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de JaneiroRio de JaneiroBrazil
  4. 4.Hospital General Roberto SantosSalvadorBrazil
  5. 5.Universidade de São PauloSao PauloBrazil
  6. 6.Hospital de Clínicas de Porto AlegrePorto AlegreBrazil
  7. 7.Centro de Hematologia e HemoterapiaUniversidade de CampinasSao PauloBrazil
  8. 8.Hospital Italiano de Buenos AiresBuenos AiresArgentina
  9. 9.Hospital Edgardo RebagliatiLimaPeru
  10. 10.Universidad de ChileSantiagoChile
  11. 11.Servicio de HematologíaUniversidad Autonoma de Nuevo Leon, Hospital Universitario “Dr. José Eleuterio Gonzalez”MonterreyMexico
  12. 12.Clinica Ruiz De Puebla, Centro de HematologiaPueblaMexico
  13. 13.Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea
  14. 14.National Organization Higashi Nagoya National HospitalNagoyaJapan
  15. 15.Beijing Chaoyang HospitalBeijingChina
  16. 16.National Taiwan University HospitalTaipeiTaiwan
  17. 17.National University Cancer InstituteSingaporeSingapore
  18. 18.Queen Mary Hospital, University of Hong Kong, ChinaPok Fu LamHong Kong
  19. 19.Chiang Mai UniversityChiang MaiThailand
  20. 20.Cedars-Sinai Medical CenterLos AngelesUSA

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