Skip to main content

Frail Patients with Newly Diagnosed Multiple Myeloma

  • Chapter
  • First Online:
Neoplastic Diseases of the Blood

Abstract

Multiple myeloma (MM) is typical of the elderly, and the median age at diagnosis is 70 years. Because of the increased life expectancy of the general population, the incidence of MM is expected to increase. Traditionally, therapy for MM patients has been selected according to age, and patients aged 65 or less are commonly assigned high-dose therapy and transplantation, while patients older than 65 years usually receive conventional chemotherapy with no transplantation. Yet, MM is highly heterogeneous, and age can no longer be the only criterion to select treatment strategy. Recently, a geriatric assessment has emerged as a valid tool to better characterize elderly patients and evaluate their frailty status. A frailty score has also been introduced by the International Myeloma Working Group, which allows a better stratification of patients into fit, intermediate, or frail categories, and consequently a more appropriate choice of therapy. A useful IT application program has been created to help clinicians quickly assess a patient’s frailty status, and further validation of the IMWG frailty score in clinical trials is necessary. Generally, fit patients can safely receive full-dose regimens, while gentler approaches with two-drug combinations and appropriate dose reductions are recommended for frail patients. Indeed, in frail patients, the aim of therapy should be controlling symptoms, maintaining an independence status and quality of life. Therefore, the achievement of a stable disease without myeloma-related symptoms related is an acceptable goal.

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

Access this chapter

Institutional subscriptions

References

  1. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364:1046–60.

    Article  CAS  PubMed  Google Scholar 

  2. Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, Edwards BK, editors. SEER cancer statistics review, 1975–2007. Bethesda: National Cancer Institute. http://seer.Cancer.Gov/csr/1975_2007/, based on November 2009 SEER data submission, posted to the SEER web site, 2010.

  3. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009;23:3–9.

    Article  CAS  PubMed  Google Scholar 

  4. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538–48.

    Article  PubMed  Google Scholar 

  5. Palumbo A, Rajkumar SV, San Miguel JF, Larocca A, Niesvizky R, Morgan G, et al. International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol. 2014;32(6):587–600.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Fayers PM, Palumbo A, Hulin C, Waage A, Wijermans P, Beksaç M, et al. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood. 2011;118(5):1239–47.

    Article  CAS  PubMed  Google Scholar 

  7. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359(9):906–17.

    Article  CAS  PubMed  Google Scholar 

  8. AnonymousRevlimid® (lenalidomide) [package insert]. Summit, NJ: Celgene Corporation; 2015.

    Google Scholar 

  9. Celgene E: Revlimid® (lenalidomide) [summary of product characteristics], 2015.

    Google Scholar 

  10. Rajkumar SV. Myeloma today: disease definitions and treatment advances. Am J Hematol. 2016;91(1):90–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Larocca A, Palumbo A. How I treat fragile myeloma patients. Blood. 2015;126(19):2179–85.

    Article  CAS  PubMed  Google Scholar 

  12. Brenner H, Gondos A, Pulte D. Expected long-term survival of patients diagnosed with multiple myeloma in 2006-2010. Haematologica. 2009;94(2):270–5.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Pulte D, Gondos A, Brenner H. Improvement in survival of older adults with multiple myeloma: results of an updated period analysis of SEER data. Oncologist. 2011;16:1600–3.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Chng WJ, Dispenzieri A, Chim CS, Fonseca R, Goldschmidt H, Lentzsch S, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014;28(2):269–77.

    Article  CAS  PubMed  Google Scholar 

  15. Kumar SK, Dispenzieri A, Gertz MA, Lacy MQ, Lust JA, Hayman SR, et al. Continued improvement in survival in multiple myeloma and the impact of novel agents [Abstract]. Blood. 2012;120:Abstract 3972.

    Google Scholar 

  16. Siegel DS, Desikan KR, Mehta J, Singhal S, Fassas A, Munshi N, et al. Age is not a prognostic variable with autotransplants for multiple myeloma. Blood. 1999;93(1):51–4.

    CAS  PubMed  Google Scholar 

  17. Lenhoff S, Hjorth M, Westin J, Brinch L, Bäckström B, Carlson K, et al. Impact of age on survival after intensive therapy for multiple myeloma: a population-based study by the Nordic Myeloma Study Group. Br J Haematol. 2006;133(4):389–96.

    Article  PubMed  Google Scholar 

  18. Yuen GJ. Altered pharmacokinetics in the elderly. Clin Geriatr Med. 1990;6(2):257–67.

    CAS  PubMed  Google Scholar 

  19. Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 2004;59(3):255–63.

    Article  PubMed  Google Scholar 

  20. Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999;341(27):2061–7.

    Article  CAS  PubMed  Google Scholar 

  21. Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27(17):2758–65.

    Article  PubMed  Google Scholar 

  22. Vestal RE. Aging and pharmacology. Cancer. 1997;80:1302–10.

    Article  CAS  PubMed  Google Scholar 

  23. Baker SD, Grochow LB. Pharmacology of cancer chemotherapy in the older person. Clin Geriatr Med. 1997;13:169–83.

    CAS  PubMed  Google Scholar 

  24. Sotaniemi EA, Arranto AJ, Pelkonen O, Pasanen M. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther. 1997;61(3):331–9.

    Article  CAS  PubMed  Google Scholar 

  25. Palumbo A, Bringhen S, Ludwig H, Dimopoulos MA, Bladé J, Mateos MV, et al. Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood. 2011;118(17):4519–29.

    Article  CAS  PubMed  Google Scholar 

  26. Repetto L, Fratino L, Audisio RA, Venturino A, Gianni W, Vercelli M, et al. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. J Clin Oncol. 2002;20(2):494–502.

    Article  PubMed  Google Scholar 

  27. Gironés R, Torregrosa D, Díaz-Beveridge R. Comorbidity, disability and geriatric syndromes in elderly breast cancer survivors. Results of a single-center experience. Crit Rev Oncol Hematol. 2010;73(3):236–45.

    Article  PubMed  Google Scholar 

  28. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–57.

    Article  CAS  PubMed  Google Scholar 

  29. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62.

    Article  PubMed  Google Scholar 

  30. Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245–51.

    Article  CAS  PubMed  Google Scholar 

  31. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.

    Article  CAS  PubMed  Google Scholar 

  32. Guralnik JM, LaCroix AZ, Everett DF, Kovar MG. Aging in the eighties: the prevalence of comorbidity and its association with disability. National Center for Health Statistics; 1989. http://www.cdc.gov/nchs/data/ad/ad170.pdf

  33. Pope AM, Tarlov AR. Disability in America. Toward a national agenda for prevention. Institute of Medicine; 1991. http://www.nap.edu/openbook.php?record_id=1579&page=R1

  34. Adams PF, Hendershot GE, Marano MA. Current estimates from the National Health Interview Survey, 1996. Vital Health Stat. 1999;200:1–203.

    Google Scholar 

  35. Fried LP, Guralnik JM. Disability in older adults: evidence regarding significance, etiology, and risk. J Am Geriatr Soc. 1997;45(1):92–100.

    Article  CAS  PubMed  Google Scholar 

  36. Fried LP, Kronmal RA, Newman AB, Bild DE, Mittelmark MB, Polak JF, Robbins JA, et al. Risk factors for 5-year mortality in older adults: the Cardiovascular Health Study. JAMA. 1998;279(8):585–92.

    Article  CAS  PubMed  Google Scholar 

  37. Reuben DB. Guidelines, evidence-based medicine, and Glidepaths: talking the talk. J Am Geriatr Soc. 2002;50(11):1905–6.

    Article  PubMed  Google Scholar 

  38. Hamaker ME, Prins MC, Stauder R. The relevance of a geriatric assessment for elderly patients with a haematological malignancy—a systematic review. Leuk Res. 2014;38:275–83.

    Article  CAS  PubMed  Google Scholar 

  39. Tucci A, Ferrari S, Bottelli C, Borlenghi E, Drera M, Rossi G. A comprehensive geriatric assessment is more effective than clinical judgment to identify elderly diffuse large cell lymphoma patients who benefit from aggressive therapy. Cancer. 2009;115(19):4547–53.

    Article  PubMed  Google Scholar 

  40. Hamaker ME, Jonker JM, de Rooij SE, Vos AG, Smorenburg CH, van Munster BC. Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review. Lancet Oncol. 2012;13:e437–44.

    Article  PubMed  Google Scholar 

  41. Extermann M, Aapro M, Bernabei R, Cohen HJ, Droz JP, Lichtman S, et al. 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. 2005;55:241–52.

    Article  PubMed  Google Scholar 

  42. Kenis C, Bron D, Libert Y, Decoster L, Van Puyvelde K, Scalliet P, et al. Relevance of a systematic geriatric screening and assessment in older patients with cancer: results of a prospective multicentric study. Ann Oncol. 2013;24(5):1306–12.

    Article  CAS  PubMed  Google Scholar 

  43. Sherman AE, Motyckova G, Fega KR, Deangelo DJ, Abel GA, Steensma D, et al. Geriatric assessment in older patients with acute myeloid leukemia: a retrospective study of associated treatment and outcomes. Leuk Res. 2013;37(9):998–1003.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015;125(13):2068–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lawton MP. Scales to measure competence in everyday activities. Psychopharmacol Bull. 1988;24(4):609–14.

    CAS  PubMed  Google Scholar 

  46. Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10):906–17.

    Article  CAS  PubMed  Google Scholar 

  47. Facon T, Hulin C, Dimopoulos MA, Belch A, Meuleman N, Mohty M, et al. A frailty scale predicts outcomes of patients with newly diagnosed multiple myeloma who are ineligible for transplant treated with continuous lenalidomide plus low-dose dexamethasone on the first trial. ASH 2015; Abstract 4239.

    Google Scholar 

  48. Durie BG, Kyle RA, Belch A, Bensinger W, Blade J, Boccadoro M, et al. Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation. Hematol J. 2003;4(6):379–98.

    Article  PubMed  Google Scholar 

  49. Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467–73.

    Article  CAS  PubMed  Google Scholar 

  50. Mehta J, Cavo M, Singhal S. How I treat elderly patients with myeloma. Blood. 2010;116(13):2215–23.

    Article  CAS  PubMed  Google Scholar 

  51. Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010;28(34):5101–9.

    Article  CAS  PubMed  Google Scholar 

  52. Palumbo A, Bringhen S, Larocca A, Rossi D, Di Raimondo F, Magarotto V, et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. J Clin Oncol. 2014;32(7):634–40.

    Article  CAS  PubMed  Google Scholar 

  53. Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, et al. Community-based phase IIIB trial of three UPFRONT Bortezomib-based myeloma regimens. J Clin Oncol. 2015;33(33):3921–9.

    Article  CAS  PubMed  Google Scholar 

  54. Magarotto V, Bringhen S, Offidani M, Benevolo G, Patriarca F, Mina R, et al. Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma. Blood. 2016;127(9):1102–8.

    Article  CAS  PubMed  Google Scholar 

  55. Larocca A, Bringhen S, Petrucci MT, Oliva S, Falcone AP, Caravita T, et al. A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma. Leukemia. 2016;30:1320. https://doi.org/10.1038/leu.2016.36. [Epub ahead of print]

    Article  CAS  PubMed  Google Scholar 

  56. Ludwig H, Durie BG, McCarthy P, Palumbo A, San Miguel J, Barlogie B, et al. IMWG consensus on maintenance therapy in multiple myeloma. Blood. 2012;119(13):3003–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012;366(19):1759–69.

    Article  CAS  PubMed  Google Scholar 

  58. Gay F, Larocca A, Wijermans P, Cavallo F, Rossi D, Schaafsma R, et al. Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood. 2011;117(11):3025–31.

    Article  CAS  PubMed  Google Scholar 

  59. Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010;11(1):29–37.

    Article  CAS  PubMed  Google Scholar 

  60. Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Grishunina M, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011;12(5):431–40.

    Article  PubMed  Google Scholar 

  61. Petrucci MT, Finsinger P, Chisini M, Gentilini F. Subcutaneous bortezomib for multiple myeloma treatment: patients’ benefits. Patient Prefer Adherence. 2014;8:939–46.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Mateos MV, San Miguel JF. Safety and efficacy of subcutaneous formulation of bortezomib versus the conventional intravenous formulation in multiple myeloma. Ther Adv Hematol. 2012;3(2):117–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Moreau P, Richardson PG, Cavo M, Orlowski RZ, San Miguel JF, Palumbo A, et al. Proteasome inhibitors in multiple myeloma: 10 years later. Blood. 2012;120(5):947–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Bringhen S, Gay F, Donato F, Troia R, Mina R, Palumbo A. Current Phase II investigational proteasome inhibitors for the treatment of multiple myeloma. Expert Opin Investig Drugs. 2014;23(9):1193–209.

    Article  CAS  PubMed  Google Scholar 

  65. Bringhen S, Mateos MV, Zweegman S, Larocca A, Falcone AP, Oriol A, et al. Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials. Haematologica. 2013;98(6):980–7.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Gay F, Palumbo A. Multiple myeloma: management of adverse events. Med Oncol. 2010;27(3):646–53.

    Article  CAS  PubMed  Google Scholar 

  67. Tonelli M, Hemmelgarn B, Reiman T, Manns B, Reaume MN, Lloyd A, et al. Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis. CMAJ. 2009;180(11):E62–71.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Neumann S, Krause SW, Maschmeyer G, Schiel X, Lilienfeld-Toal v, Infectious Diseases M. Working Party (AGIHO); German Society of Hematology and Oncology (DGHO). Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematological malignancies and solid tumors: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol. 2013;92(4):433–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. de Naurois J, Novitzky-Basso I, Gill MJ, Marti FM, Cullen MH, Roila F. Management of febrile neutropenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2010;21(Suppl. 5):v252–6.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonio Palumbo M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Cite this chapter

Larocca, A., Palumbo, A. (2018). Frail Patients with Newly Diagnosed Multiple Myeloma. In: Wiernik, P., Dutcher, J., Gertz, M. (eds) Neoplastic Diseases of the Blood. Springer, Cham. https://doi.org/10.1007/978-3-319-64263-5_27

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-64263-5_27

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-64262-8

  • Online ISBN: 978-3-319-64263-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics