Skip to main content
SpringerLink
Log in

Treatment patterns and outcomes in real-world transplant-ineligible patients newly diagnosed with multiple myeloma

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Despite the significant proportion of older patients with newly diagnosed multiple myeloma (MM), most clinical trials driving therapeutic decisions in routine practice include younger and presumably healthier patients than those in the real world. Furthermore, longitudinal studies suggest that elderly, transplant-ineligible patients with MM are not benefitting enough from new anti-MM agents. We retrospectively analyzed the profile of and treatment patterns and outcomes in 675 transplant-ineligible patients with MM who started frontline therapy in routine practice. The mean (SD) age was 75.6 (6.7) years; 152 (47.4%) had Eastern Cooperative Oncology Group performance status (ECOG PS) 2–4, and 73 (25.1%) had high cytogenetic risk. The most frequent frontline therapy was non-VMP bortezomib-based regimens (n=207; 30.7%), which were more frequent among patients with ECOG PS 0/1 and higher risk (e.g., international staging system (ISS) stage III, severely impaired glomerular filtrate rate (GFR), high lactate dehydrogenase (LDH), and high-risk cytogenetics); 185 patients (27.4%) started an attenuated (lite) VMP regimen, and 159 (23.6%) a VMP (VISTA) regimen. Median progression-free survival and overall survival (OS) were 15.3 months (95%CI 14.0–16.9) and 33.5 months (95%CI 29.1–37.2), respectively; 405 patients (78.2%) achieved partial response or better. Age, ECOG PS, ISS stage, serum LDH, GFR, cytogenetic risk, and treatment regimen significantly influenced OS. In this study, a remarkable proportion of transplant-ineligible patients with MM were older, frontline regimens were highly heterogeneous, and patients at higher risk often received less efficacious combinations. These findings suggest that clinicians have limited objective criteria for therapeutic decisions for this patient group.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

Additional data used in this study are available from the corresponding author on reasonable request.

Code availability

Not applicable

References

  1. Kazandjian D (2016) Multiple myeloma epidemiology and survival: a unique malignancy. Semin Oncol 43:676–681. https://doi.org/10.1053/j.seminoncol.2016.11.004

    Article  PubMed  PubMed Central  Google Scholar 

  2. Palumbo A, Anderson K (2011) Multiple myeloma. N Engl J Med 364:1046–1060. https://doi.org/10.1056/NEJMra1011442

    Article  CAS  PubMed  Google Scholar 

  3. Bladé J, Kyle RA, Greipp PR (1996) Multiple myeloma in patients younger than 30 years: report of 10 cases and review of the literature. Arch Intern Med 156:1463–1468

    Article  PubMed  Google Scholar 

  4. Howlader N, Noone A, Krapcho M, et al (2015) Cancer Statistics Review, 1975-2013. In: Natl. Cancer Institute. Bethesda, MD,. https://seer.cancer.gov/archive/csr/1975_2013/. Accessed 2 Nov 2019

  5. Palumbo A, Bringhen S, Ludwig H, Dimopoulos MA, Bladé J, Mateos MV, Rosiñol L, Boccadoro M, Cavo M, Lokhorst H, Zweegman S, Terpos E, Davies F, Driessen C, Gimsing P, Gramatzki M, Hàjek R, Johnsen HE, Leal da Costa F, Sezer O, Spencer A, Beksac M, Morgan G, Einsele H, San Miguel JF, Sonneveld P (2011) Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood 118:4519–4529

    Article  CAS  PubMed  Google Scholar 

  6. Ríos-Tamayo R, Sáinz J, Martínez-López J, Puerta JM, Chang DYL, Rodríguez T, Garrido P, de Veas JLG, Romero A, Moratalla L, López-Fernández E, González PA, Sánchez MJ, Jiménez-Moleón JJ, Jurado M, Lahuerta JJ (2016) Early mortality in multiple myeloma: the time-dependent impact of comorbidity: a population-based study in 621 real-life patients. Am J Hematol 91:700–704. https://doi.org/10.1002/ajh.24389

    Article  PubMed  Google Scholar 

  7. Verelst S, Karim-Kos H, Blommestein H, Sonneveld P (2012) Are we making progress? Survival in plasma cell malignancies in the era of novel treatments a population based study of 17.790 patients in The Netherlands. In: 17th Congress of the European Hematology Association (EHA), Amsterdam (The Netherlands). Haematologica. p 242

  8. Schaapveld M, Visser O, Siesling S, Schaar CG, Zweegman S, Vellenga E (2010) Improved survival among younger but not among older patients with multiple myeloma in the Netherlands, a population-based study since 1989. Eur J Cancer 46:160–169

    Article  PubMed  Google Scholar 

  9. Moureau, Moreau P, San Miguel J et al (2017) Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 28:iv52–iv61. https://doi.org/10.1093/annonc/mdx096

    Article  Google Scholar 

  10. Mikhael J, Ismaila N, Cheung MC, Costello C, Dhodapkar MV, Kumar S, Lacy M, Lipe B, Little RF, Nikonova A, Omel J, Peswani N, Prica A, Raje N, Seth R, Vesole DH, Walker I, Whitley A, Wildes TM, Wong SW, Martin T (2019) Treatment of multiple myeloma: ASCO and CCO joint clinical practice guideline. J Clin Oncol 37:1228–1263. https://doi.org/10.1200/JCO.18.02096

    Article  PubMed  Google Scholar 

  11. Zanwar S, Abeykoon JP, Kapoor P (2019) Challenges and strategies in the management of multiple myeloma in the elderly population. Curr Hematol Malig Rep 14:70–82. https://doi.org/10.1007/s11899-019-00500-4

    Article  PubMed  Google Scholar 

  12. Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BGM, Dimopoulos MA, Landgren O, San Miguel JF, Richardson P, Sonneveld P, Rajkumar SV (2015) Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood 125:2068–2074. https://doi.org/10.1182/blood-2014-12-615187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tucci A, Ferrari S, Bottelli C et al (2009) A comprehensive geriatric assessment is more effective than clinical judgment to identify elderly diffuse large cell lymphoma patients who benefit from aggressive therapy. Cancer Interdiscip Int J Am Cancer Soc 115:4547–4553

    Google Scholar 

  14. Extermann M, Aapro M, Bernabei R, Cohen HJ, Droz JP, Lichtman S, Mor V, Monfardini S, Repetto L, Sørbye L, Topinkova E (2005) Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol 55:241–252

    Article  PubMed  Google Scholar 

  15. Bonanad S, De la Rubia J, Gironella M et al (2015) Development and psychometric validation of a brief comprehensive health status assessment scale in older patients with hematological malignancies: The GAH Scale. J Geriatr Oncol 6:353–361. https://doi.org/10.1016/j.jgo.2015.03.003

    Article  CAS  PubMed  Google Scholar 

  16. Bergin K, McQuilten Z, Moore E et al (2017) Myeloma in the real world: what is really happening? Clin Lymphoma, Myeloma Leuk 17:133–144.e1. https://doi.org/10.1016/j.clml.2016.12.002

    Article  Google Scholar 

  17. Song X, Cong Z, Wilson K (2016) Real-world treatment patterns, comorbidities, and disease-related complications in patients with multiple myeloma in the United States. Curr Med Res Opin 32:95–103. https://doi.org/10.1185/03007995.2015.1105202

    Article  CAS  PubMed  Google Scholar 

  18. Mateos MV, Martínez-López J, Hernández MT, Ocio EM, Rosiñol L, Martínez R, Teruel AI, Gutiérrez NC, Martín Ramos ML, Oriol A, Bargay J, Bengoechea E, González Y, Pérez de Oteyza J, Gironella M, Encinas C, Martín J, Cabrera C, Paiva B, Cedena MT, Puig N, Bladé J, Lahuerta JJ, San-Miguel J (2016) Sequential vs alternating administration of VMP and Rd in elderly patients with newly diagnosed MM. Blood 127:420–425. https://doi.org/10.1182/blood-2015-08-666537

    Article  CAS  PubMed  Google Scholar 

  19. Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Bladé J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H (2016) International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 17:e328–e346

    Article  PubMed  Google Scholar 

  20. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H, Richardson PG (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 359:906–917. https://doi.org/10.1056/NEJMoa0801479

    Article  CAS  PubMed  Google Scholar 

  21. 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 (2014) Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med 371:906–917. https://doi.org/10.1056/NEJMoa1402551

    Article  CAS  PubMed  Google Scholar 

  22. Shah JJ, Abonour R, Gasparetto C et al (2017) Analysis of common eligibility criteria of randomized controlled trials in newly diagnosed multiple myeloma patients and extrapolating outcomes. Clin Lymphoma, Myeloma Leuk 17:575–583.e2. https://doi.org/10.1016/j.clml.2017.06.013

    Article  Google Scholar 

  23. Yong K, Delforge M, Driessen C, Fink L, Flinois A, Gonzalez-McQuire S, Safaei R, Karlin L, Mateos MV, Raab MS, Schoen P, Cavo M (2016) Multiple myeloma: patient outcomes in real-world practice. Br J Haematol 175:252–264. https://doi.org/10.1111/bjh.14213

    Article  PubMed  PubMed Central  Google Scholar 

  24. Blommestein HM, Verelst SGR, de Groot S, Huijgens PC, Sonneveld P, Uyl-de Groot CA (2016) A cost-effectiveness analysis of real-world treatment for elderly patients with multiple myeloma using a full disease model. Eur J Haematol 96:198–208. https://doi.org/10.1111/ejh.12571

    Article  PubMed  Google Scholar 

  25. Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, de Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A (2010) Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood 116:4745–4753. https://doi.org/10.1182/blood-2010-07-294983

    Article  CAS  PubMed  Google Scholar 

  26. Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, de Paz R, García-Laraña J, Bengoechea E, Martín A, Mediavilla JD, Palomera L, de Arriba F, González Y, Hernández JM, Sureda A, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Cibeira MT, Ramos MLM, Vidriales MB, Paiva B, Montalbán MA, Lahuerta JJ, Bladé J, Miguel JFS (2010) Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myelom. Lancet Oncol 11:934–941. https://doi.org/10.1016/S1470-2045(10)70187-X

    Article  CAS  PubMed  Google Scholar 

  27. Ziogas DC, Dimopoulos MA, Kastritis E (2018) Prognostic factors for multiple myeloma in the era of novel therapies. Expert Rev Hematol 11:863–879. https://doi.org/10.1080/17474086.2018.1537776

    Article  CAS  PubMed  Google Scholar 

  28. 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 8:109. https://doi.org/10.1038/s41408-018-0141-0

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kristinsson SY, Landgren O, Dickman PW, Derolf ÅR, 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 25:1993–1999. https://doi.org/10.1200/JCO.2006.09.0100

    Article  PubMed  Google Scholar 

  30. 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 28:830–834. https://doi.org/10.1200/JCO.2009.25.4177

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Josep Puig and Gerard Carot-Sans provided statistical and medical writing support, respectively, on behalf of BioClever, 2005.

Funding

The study was promoted, sponsored, and funded by Celgene, a Bristol Myers Squibb Company.

Author information

Authors and Affiliations

  1. Department of Hematology, Hospital Universitario Doctor Peset, Av. de Gaspar Aguilar, 90 46017, Valencia, Spain

    María José Cejalvo & Javier de la Rubia

  2. Department of Hematology, Institut Català d’Oncologia, Hospital Duran i Reynals, Barcelona, Spain

    Gabriela Bustamante

  3. Department of Hematology, Hospital de Cabueñes, Gijón, Spain

    Esther González

  4. Department of Hematology, Hospital Álvaro Cunqueiro, Vigo, Spain

    Judith Vázquez-Álvarez

  5. Department of Hematology, Hospital Universitario Virgen de la Victoria, Málaga, Spain

    Ricarda García

  6. Department of Hematology, Hospital Universitario Central de Asturias, Oviedo, Spain

    Ángel Ramírez-Payer

  7. Department of Hematology, Hospital Universitario de Álava, Vitoria-Gasteiz, Spain

    Ernesto Pérez-Persona

  8. Department of Hematology, Hospital del Mar, Barcelona, Spain

    Eugenia Abella

  9. Department of Hematology, Hospital de Jerez, Jerez de la Frontera, Spain

    Sebastián Garzón

  10. Department of Hematology, Hospital Arnau de Vilanova, Lleida, Spain

    Antoni García

  11. Department of Hematology, Hospital Universitario y Politécnico La Fe, Valencia & CIBERONC, Instituto de Salud Carlos III, Valencia, Spain

    Isidro Jarque

  12. Department of Hematology, Hospital de Santiago, Santiago de Compostela, Spain

    Marta Sonia González

  13. Department of Hematology, Hospital Son Espases, Palma de Mallorca, Spain

    Antonia Sampol

  14. Department of Hematology, Fundació Althaia, Manresa, Spain

    Cristina Motlló

  15. Department of Hematology, Hospital Mútua de Terrassa, Terrassa, Spain

    Josep María Martí

  16. Department of Hematology, Hospital Universitario Carlos Haya, Málaga, Spain

    Magdalena Alcalá

  17. Department of Hematology, Hospital Universitario Virgen de la Macarena, Sevilla, Spain

    Rafael Duro

  18. Department of Hematology, Hospital Universitario de Girona Doctor Josep Trueta, Girona, Spain

    Yolanda González

  19. Department of Hematology, Complejo Hospitalario Universitario de Ourense, Ourense, Spain

    José Luis Sastre

  20. Department of Hematology, Hospital Universitario Joan XXIII, Tarragona, Spain

    Josep Sarrà

  21. Celgene S.L.U., Bristol-Myers Squibb Company, Madrid, Spain

    Giselle Lostaunau & Rocío López

  22. Departamento de Medicina Interna y Odontología, Universidad Católica de Valencia, Valencia, Spain

    Javier de la Rubia

Authors
  1. María José Cejalvo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriela Bustamante
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Esther González
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Judith Vázquez-Álvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ricarda García
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ángel Ramírez-Payer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ernesto Pérez-Persona
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eugenia Abella
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sebastián Garzón
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Antoni García
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Isidro Jarque
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Marta Sonia González
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Antonia Sampol
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Cristina Motlló
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Josep María Martí
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Magdalena Alcalá
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Rafael Duro
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Yolanda González
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. José Luis Sastre
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Josep Sarrà
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Giselle Lostaunau
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Rocío López
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Javier de la Rubia
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The study was conceived and designed by MJC, GL, RL, and JR. MJC, GB, EG, JV-A, RG, AR-P, EP-P, EA, SG, AG, IJ, MSG, AS, CM, JMM, MA, and JR made substantial contributions to data collection. GL, RL, and JR made substantial contributions to data interpretation. JR contributed to manuscript drafting and review. MJC, GB, EG, JV-A, RG, AR-P, EP-P, EA, SG, AG, IJ, MSG, AS, CM, JMM, MA, GL, and RL revised critically the subsequent manuscript drafts. All co-authors approved the final version of the manuscript.

Corresponding author

Correspondence to Javier de la Rubia.

Ethics declarations

Ethics approval

The study protocol was approved by the independent ethics committee of the University Hospital Dr. Peset (Valencia, Spain)

Consent to participate

All patients provided written consent to include their data in the study records.

Consent for publication

Not applicable

Conflicts of interest

María José Cejalvo has received research support from Celgene, a Bristol-Meyers Squibb Company. Ernesto Pérez-Persona reports non-financial support and personal fees from Celgene, a Bristol-Meyers Squibb Company, Roche, Janssen, Amgen; and personal fees from Abbvie and non-financial support from Jazz Pharmaceuticals. Sebastián Garzón has received grants and personal fees from Celgene, a Bristol-Meyers Squibb Company, Amgen, Janssen, and Takeda. Isidro Jarque has received speaker fees from and/or served on advisory boards for Abbie, Alexion, Amgen, Bristol-Myers Squibb/Celgene, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, and Takeda/Shire. Giselle Lostaunau and Rocío López are employees of Celgene, a Bristol-Meyers Squibb Company. Javier de la Rubia has received research support from Celgene, a Bristol-Meyers Squibb Company, has received a speaker honorarium, and has served on advisory boards for Amgen, Celgene, a Bristol-Meyers Squibb Company, Janssen, and Takeda. The other authors, Gabriela Bustamante, Esther González, Judith Vázquez-Álvarez, Ricarda García, Ángel Ramírez-Payer, Eugenia Abella, Antoni García, Marta Sonia González, Antonia Sampol, Cristina Motlló, Josep María Martí, Magdalena Alcalá, Rafael Duro, Yolanda González, José Luis Sastre, and Josep Sarra declare they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(PDF 429 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cejalvo, M.J., Bustamante, G., González, E. et al. Treatment patterns and outcomes in real-world transplant-ineligible patients newly diagnosed with multiple myeloma. Ann Hematol 100, 1769–1778 (2021). https://doi.org/10.1007/s00277-021-04529-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-021-04529-5

Keywords

Search

Navigation