Skip to main content

Advertisement

SpringerLink
Log in

Multiple Myeloma: Treatment is Getting Individualized

  • Review Article
  • Published:
Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

Multiple myeloma (MM) is a heterogeneous disease with varied outcome. The novel agents including two major classes of drugs; the immunomodulatory drugs and the proteasome inhibitors with unprecedented response rates, have replaced conventional chemotherapy. With monoclonal antibodies on the horizon, outcome of this disorder will further improve. Progression in risk stratification systems has made it possible to predict the disease course as well as outcome in myeloma patients with disease categorization into low to high risk. In addition, detection of minimal residual disease by serum free light chain assay, flow cytometry, molecular techniques like polymerase chain reaction and positron emission tomography scan is playing an important role in modifying the treatment. An extensive research in the disease biology has improved our knowledge regarding interplay between myeloma cells and elements of the bone marrow microenvironment which contribute to sustain proliferation and survival as well as de novo drug resistance. Again, insight into the role of genetic and epigenetic interactions in MM has exposed new molecular targets. All these have opened the gateway for novel therapeutic strategies with focus on risk based individualized therapy.

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

Similar content being viewed by others

References

  1. 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Kumar SK, Mikhael JR, Buadi FK, Dingli D, Dispenzieri A, Fonseca R et al (2009) Management of newly diagnosed symptomatic multiple myeloma: updated mayo stratification of myeloma and risk-adapted therapy (mSMART) consensus guidelines. Mayo Clin Proc 84(12):1095–1110

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Ghalaut PS, Chaudhuri S, Singh R (2013) Recent advances in diagnosis and management of multiple myeloma: an update. In: The Association of Physicians of India, Medicine Update 2013, Section 10 Hematology, Chapter 80, pp 360–365

  4. Ries LAG, Melbert D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, et al (2007) SEER Cancer Statistics Review, 1975–2004. National Cancer Institute, Bethesda [online]. Available from http://seer.cancer.gov/csr/1975_2004/. Accessed Nov 2012

  5. Programme National Cancer Registry (2005) Two year report of the population based cancer registries 1999–2000. Indian Council of Medical Research, New Delhi

    Google Scholar 

  6. Kumar L, Verma R, Radhakrishnan VR (2010) Recent advances in the management of multiple myeloma. Natl Med J India 23(4):210–218

    PubMed  Google Scholar 

  7. Alexanian R, Barlogie B, Tucker S (1990) VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol 33:86–89

    Article  CAS  PubMed  Google Scholar 

  8. Forgeson GV, Selby P, Lakhani S, Zulian G, Viner C, Maitland J et al (1988) Infused vincristine and adriamycin with high dose methylprednisolone (VAMP) in advanced previously treated multiple myeloma patients. Br J Cancer 58:469–473

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Durie BG, Salmon SE (1975) A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment and survival. Cancer 36:842–854

    Article  CAS  PubMed  Google Scholar 

  10. Greipp PR, Miguel JS, Durie BG, Crowley JJ, Barlogie B, Bladé J et al (2005) International staging system for multiple myeloma. J Clin Oncol 23:3412–3420

    Article  PubMed  Google Scholar 

  11. Munshi NC, Anderson KC, Bergsagel PL, Shaughnessy J, Palumbo A, Durie B et al (2011) Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood 117(18):4696–4700

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Niels WCJ, Donk VD, Sonneveld P (2014) Diagnosis and risk stratification in multiple myeloma. Hematol Oncol Clin N Am 28:791–813

    Article  Google Scholar 

  13. Girnius S, Munshi NC (2013) Individualized therapy in multiple myeloma: are we there? Semin Oncol 40(5):567–576

    Article  PubMed  Google Scholar 

  14. Flactif M, Zandecki M, Laï JL, Bernardi F, Obein V, Bauters F et al (1995) Interphase fluorescence in situ hybridization (FISH) as a powerful tool for the detection of aneuploidy in multiple myeloma. Leukemia 9:2109–2114

    CAS  PubMed  Google Scholar 

  15. Chng WJ, Dispenzieri A, Chim CS, Fonseca R, Goldschmidt H, Lentzsch S et al (2014) IMWG consensus on risk stratification in multiple myeloma. Leukemia 28:269–277

    Article  CAS  PubMed  Google Scholar 

  16. Ross FM, vet-Loiseau H, Ameye G, Gutiérrez NC, Liebisch P, O’Connor S et al (2012) Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders. Haematologica 97(8):1272–1277

    Article  PubMed Central  PubMed  Google Scholar 

  17. Avet-Loiseau H, Li C, Magrangeas F, Gouraud W, Charbonnel C, Harousseau JL et al (2009) Prognostic significance of copy-number alterations in multiple myeloma. J Clin Oncol 27:4585–4590

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Broyl A, Hose D, Lokhorst H, Knegt Y, Peeters J, Jauch A et al (2010) Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients. Blood 16(14):2543–2553

    Article  Google Scholar 

  19. Chi J, Ballabio E, Chen X, Kušec R, Taylor S, Hay D et al (2011) MicroRNA expression in multiple myeloma is associated with genetic subtype, isotype and survival. Biol Direct 6:23

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Anderson KC (2012) The 39th David A. Karnofsky Lecture: bench-to-bedside translation of targeted therapies in multiple myeloma. J Clin Oncol 30:445–452

    Article  CAS  PubMed  Google Scholar 

  21. Munshi NC, Anderson KC (2013) New strategies in the treatment of multiple myeloma. Clin Cancer Res. doi:10.1158/1078-0432.CCR-12-1881

    Google Scholar 

  22. Bladé J, Sonneveld P, San Miguel JF, Sutherland HJ, Hajek R, Nagler A et al (2011) Efficacy and safety of pegylated liposomal doxorubicin in combination with bortezomib for multiple myeloma: effects of adverse prognostic factors on outcome. Clin Lymphoma Myeloma Leuk 11(1):44–49

    Article  PubMed  Google Scholar 

  23. Lacy MQ, Hayman SR, Gertz MA, Dispenzieri A, Buadi F, Kumar S et al (2009) Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol 27:5008–5014

    Article  CAS  PubMed  Google Scholar 

  24. Rajkumar SV, Gahrton G, Bergsagel PL (2011) Approach to the treatment of multiple myeloma: a clash of philosophies. Blood 118(12):3205–3211

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Lonial S, Vij R, Harousseau JL, Facon T, Moreau P, Mazumder A et al (2012) Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol 30:1953–1959

    Article  CAS  PubMed  Google Scholar 

  26. Mailankody S, Korde N, Lesokhin AM, Lendvai N, Hassoun H, Stetler-Stevenson M et al (2015) Minimal residual disease in multiple myeloma: bringing the bench to the bedside. Nat Rev Clin Oncol 12:286–295. doi:10.1038/nrclinonc.2014.239

    Article  PubMed  Google Scholar 

  27. Ladetto M, Pagliano G, Ferrero S, Cavallo F, Drandi D, Santo L et al (2010) Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol 28(12):2077–2084

    Article  CAS  PubMed  Google Scholar 

  28. Munshi NC, Anderson KC (2013) Minimal residual disease in multiple myeloma. J Clin Oncol 31(20):2523–2526

    Article  PubMed  Google Scholar 

  29. Martinez-Lopez J, Lahuerta JJ, Pepin F, González M, Barrio S, Ayala R et al (2014) Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma. Blood 123(20):3073–3079

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Walker R, Barlogie B, Haessler J, Tricot G, Anaissie E, Shaughnessy JD Jr et al (2007) Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. J Clin Oncol 25:1121–1128

    Article  PubMed  Google Scholar 

  31. Bartel TB, Haessler J, Brown TLY, Shaughnessy JD Jr, van Rhee F, Anaissie E et al (2009) F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma. Blood 114:2068–2076

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Puente PDL, Muz B, Azab F, Luderer M, Azab AK (2014) Molecularly targeted therapies in multiple myeloma. Hindawi Publishing Corporation Leukemia Research and Treatment, Article ID 976567. doi:10.1155/2014/976567

  33. Dimopoulos K, Gimsing P, Gronbaek K (2014) The role of epigenetics in the biology of multiple myeloma. Blood Cancer Journal 4:e207

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Mitsiades CS, Mitsiades NS, McMullan CJ, Poulaki V, Shringarpure R, Hideshima T et al (2004) Transcriptional signature of histone deacetylase inhibition in multiple myeloma: biological and clinical implications. Proc Natl Acad Sci USA 101:540–545

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Jagannath S, Dimopoulos MA, Lonial S (2010) Combined proteasome and histone deacetylase inhibition: A promising synergy for patients with relapsed/refractory multiple myeloma. Leuk Res 34:1111–1118

    Article  CAS  PubMed  Google Scholar 

  36. Shi Y, Reiman T, Li W, Maxwell CA, Sen S, Pilarski L et al (2007) Targeting aurora kinases as therapy in multiple myeloma. Blood 109:3915–3921

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Hideshima T, Catley L, Raje N, Chauhan D, Podar K, Mitsiades C et al (2007) Inhibition of Akt induces significant downregulation of survivin and cytotoxicity in human multiple myeloma cells. Br J Haematol 138:783–791

    Article  CAS  PubMed  Google Scholar 

  38. Khan SA, Cohen AD (2011) Experimental approaches in the treatment of multiple myeloma. Ther Adv Hematol 2(4):213–230

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Siegel D, Jagannath S, Vesole DH, Borello I, Mazumder A, Mitsiades C et al (2011) A phase 1 study of IPI-504 (retaspimycin hydrochloride) in patients with relapsed or relapsed and refractory multiple myeloma. Leuk Lymphoma 52:2308–2315

    Article  CAS  PubMed  Google Scholar 

  40. Richardson PG, Badros AZ, Jagannath S, Tarantolo S, Wolf JL, Albitar M et al (2010) Tanespimycin with bortezomib: activity in relapsed/refractory patients with multiple myeloma. Br J Haematol 150:428–437

    PubMed Central  CAS  PubMed  Google Scholar 

  41. Neri P, Kumar S, Fulciniti MT, Vallet S, Chhetri S, Mukherjee S et al (2007) Neutralizing B cell activating factor antibody improves survival and inhibits osteoclastogenesis in a severe combined immunodeficient human multiple myeloma model. Clin Cancer Res 13:5903–5909

    Article  CAS  PubMed  Google Scholar 

  42. Tai YT, Li XF, Breitkreutz I, Song W, Neri P, Catley L et al (2006) Role of B-cell-activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow microenvironment. Cancer Res 66:6675–6682

    Article  CAS  PubMed  Google Scholar 

  43. Zhu YX, Tiedemann R, Shi CX, Yin H, Schmidt JE, Bruins LA et al (2011) RNAi screen of the druggable genome identifies modulators of proteasome inhibitor sensitivity in myeloma including CDK5. Blood 117:3847–3857

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Hideshima T, Anderson KC (2002) Molecular mechanisms of novel therapeutic approaches for multiple myeloma. Nat Rev Cancer 2:927–937

    Article  CAS  PubMed  Google Scholar 

  45. Kroger N, Badbaran A, Zabelina T, Ayuk F, Wolschke C, Alchalby H et al (2013) Impact of high-risk cytogenetics and achievement of molecular remission on long-term freedom from disease after autologous-allogenic tandem transplantation in multiple myeloma. Biol Blood Marrow Transpl 19:398–404

    Article  Google Scholar 

  46. Sugumar D, Keller J, Vij R (2015) Targeted treatments for multiple myeloma: specific role of carfilzomib. Pharmgenomics Pers Med 8:23–33

    PubMed Central  PubMed  Google Scholar 

  47. Fouquet G, Bories C, Guidez S, Renaud L, Herbaux C, Javed S et al (2014) Expert reviews pomalidomide for multiple myeloma. Expert Rev Hematol. Early online, 1–13 (2014). Available from: http://szpiczak.org/lang/aktualnosci/komunikaty/pdf/rok_2014/17474086_2014_966074.pdf

  48. Richardson PG, Laubach JP, Munshi NC, Anderson KC (2014) Early or delayed transplantation for multiple myeloma in the era of novel therapy: does one size fit all? Hematol Am Soc Hematol Educ Progr 1:255–261

    Article  Google Scholar 

  49. Lohr JG, Stojanov P, Carter SL, Cruz-Gordillo P, Lawrence MS, Auclair D et al (2014) Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell 25(1):91–101

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Xie Z, Chng WJ (2014) MMSET: role and therapeutic opportunities in multiple myeloma. BioMed Res Int, Article ID 636514

  51. Misso G, Zappavigna S, Castellano M, Rosa GD, Martino MT, Tagliaferri P (2013) Emerging pathways as individualized therapeutic target of multiple myeloma. Expert Opin Biol Ther 13(1):S95–S109

    Article  CAS  PubMed  Google Scholar 

  52. Dimopoulos MA, Kastritis E, Christoulas D, Migkou M, Gavriatopoulou M, Gkotzamanidou M et al (2010) Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies. Leukemia 24(10):1769–1778

    Article  CAS  PubMed  Google Scholar 

  53. Nahi H, Sutlu T, Jansson M, Alici E, Gahrton G (2010) Clinical impact of chromosomal aberrations in multiple myeloma. J Intern Med. doi:10.1111/j.1365-2796.2010.02324.x

    PubMed  Google Scholar 

  54. Smadja NV, Bastard C, Brigaudeau C, Leroux D, Fruchart C (2001) Hypodiploidy is a major prognostic factor in multiple myeloma. Blood 98(7):2229–2238

    Article  CAS  PubMed  Google Scholar 

  55. Rajkumar SV (2012) Doublets, triplets or quadruplets on novel agents in the treatment of newly diagnosed myeloma. ASH Educ Book 1:354–361. doi:10.1182/asheducation-2012.1.354

    Google Scholar 

  56. Scheid C, Reece D, Beksac M, Spencer A, Callander N, Sonneveld P et al (2015) Phase 2 study of dovitinib in patients with relapsed or refractory multiple myeloma with or without t(4;14) translocation. Eur J Haematol. doi:10.1111/ejh.12491

    Google Scholar 

  57. Leow CC, Gerondakis S, Spencer A (2013) MEK inhibitors as a chemotherapeutic intervention in multiple myeloma. Blood Cancer J 3:e105. doi:10.1038/bcj.2013.1

    Article  Google Scholar 

  58. Herath NI, Rocques N, Garancher Eychène A, Pouponnot C (2014) GSK3-mediated MAF phosphorylation in multiple myeloma as a potential therapeutic target. Blood Cancer J 4:e175. doi:10.1038/bcj.2013.67

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Biran N, Jagannath S, Chari A (2013) Risk stratification in multiple myeloma, part 1: characterization of high-risk disease. Clin Adv Hematol Oncol 11(8):489–503

    PubMed  Google Scholar 

  60. Hanamura I, Stewart JP, Huang Y, Zhan F, Santra M, Sawyer JR 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 tandemstem-cell transplantation. Blood 108:1724–1732

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Shaughnessy J (2005) Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma. Hematology 10(Suppl 1):117–126

    Article  CAS  PubMed  Google Scholar 

  62. Yu W, Li J, Chen L (2014) Prognostic value and efficacy evaluation of novel drugs for cytogenetic aberrations in multiple myeloma: a meta-analysis. Int J Clin Exp Med 7(11):4051–4062

    PubMed Central  PubMed  Google Scholar 

  63. 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

    Article  CAS  PubMed  Google Scholar 

  64. Roussou M, Kastritis E, Migkou M, Psimenou E, Grapsa I, Matsouka C et al (2008) Treatment of patients with multiple myeloma complicated by renal failure with bortezomib-based regimens. Leuk Lymphoma 49(5):890–895

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Professional medical writing support and editorial assistance was provided by DiagnoSearch Life Sciences (P) Ltd., funded by Bristol-Myers Squibb.

Author information

Authors and Affiliations

  1. Department of Haematology, Bombay Hospital Institute of Medical Sciences, Mumbai, India

    M. B. Agarwal

Authors
  1. M. B. Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. B. Agarwal.

Ethics declarations

Conflict of Interest

The author did not receive financial compensation for authoring the manuscript.

Additional information

Communicated by Haraprasad Pati.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Agarwal, M.B. Multiple Myeloma: Treatment is Getting Individualized. Indian J Hematol Blood Transfus 32, 3–9 (2016). https://doi.org/10.1007/s12288-015-0575-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12288-015-0575-5

Keywords

Search

Navigation