Skip to main content
SpringerLink
Log in

Tailoring treatment in myeloma: are there clues from biology?

  • short review
  • Published:
memo - Magazine of European Medical Oncology Aims and scope Submit manuscript

Abstract

Cytogenetic data have established relevance for prognostication in myeloma. Also, certain chromosomal aberrations were associated with an increased risk of progression of smoldering myeloma to active disease. The impact of cytogenetic and molecular data on treatment decisions is however limited. Myeloma patients with a t(4;14) have been shown to benefit from bortezomib treatment, while thalidomide treatment has a detrimental effect in cases with del17p13. The discovery of marked intraclonal heterogeneity has influence on therapeutic concepts to treat plasma cell disease, but so far no relevance for guiding treatment in individual cases. Cereblon is the molecular target of immunomodulatory substances, and expression levels have been linked to treatment outcome under thalidomide, lenalidomide, and pomalidomide treatment. Alternative splicing has been described for cereblon, and relevance of different isoforms for drug sensitivity is currently under study. So far no reliable clinical test exists to predict for response to immunomodulatory substances.

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. Neben K, Jauch A, Hielscher T, et al. Progression in smoldering myeloma is independently determined by the chromosomal abnormalities del(17p), t(4;14), gain 1q, hyperdiploidy, and tumor load. J Clin Oncol. 2013;31(34):4325–32.

    Article  PubMed  Google Scholar 

  2. Rajkumar SV, Gupta V, Fonseca R, et al. Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma. Leukemia. 2013;27(8):1738–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. López-Corral L, Mateos MV, Corchete LA, et al. Genomic analysis of high-risk smoldering multiple myeloma. Haematologica. 2012;97(9):1439–43.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–48.

    Article  PubMed  Google Scholar 

  5. Chng WJ, Dispenzieri A, Chim CS, et al. International Myeloma Working Group. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014;28(2):269–77.

    Article  CAS  PubMed  Google Scholar 

  6. Avet-Loiseau H, Leleu X, Roussel M, et al. Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol. 2010;28(30):4630–4.

    Article  CAS  PubMed  Google Scholar 

  7. Cavo M, Tacchetti P, Patriarca F, et al. GIMEMA Italian Myeloma Network. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010;376(9758):2075–85.

    Article  CAS  PubMed  Google Scholar 

  8. San Miguel JF, Schlag R, Khuageva NK, et al. VISTA Trial Investigators. 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 

  9. Neben K, Lokhorst HM, Jauch A, et al. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012;119(4):940–8.

    Article  CAS  PubMed  Google Scholar 

  10. Cavo M, Sonneveld P, Moreau P, et al. Impact of bortezomib incorporated into autotransplantation on outcomes of myeloma patients with high-risk cytogenetics: an integrated analysis of 1894 patients enrolled in four European Phase 3 studies. Blood (ASH Annual Meeting Abstracts). 2012;120:749.

  11. Knop S, Liebisch P, Hebart H, et al. Autologous followed by allogeneic versus tandem-autologous stem cell transplant in newly diagnosed FISH-del13q myeloma. Blood (ASH Annual Meeting Abstracts). 2014; 124: 43.

  12. Morgan GJ, Gregory WM, Davies FE, et al. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood. 2012;119(1):7–15.

    Article  CAS  PubMed  Google Scholar 

  13. Leleu X, Karlin L, Macro M, et al. Pomalidomide plus low-dose dexamethasone in relapsed or refractory multiple myeloma (RRMM) With deletion (del)17p and/Or translocation t(4;14). Blood (ASH Annual Meeting Abstracts). 2013;122:689.

  14. Palumbo A, Bringhen S, Rossi D, 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 

  15. Gay F, Cerrato C, Hajek R, et al. Impact of Autologous Transplantation Vs. Chemotherapy Plus Lenalidomide in Newly Diagnosed Myeloma According to Patient Prognosis: Results of a Pooled Analysis of 2 Phase III Trials. Blood (ASH Annual Meeting Abstracts). 2014;124:198.

  16. Brioli A, Melchor L, Cavo M, Morgan GJ. The impact of intra-clonal heterogeneity on the treatment of multiple myeloma. Br J Haematol. 2014;165(4):441–54.

    Article  PubMed  Google Scholar 

  17. Oerlemans R, Franke NE, Assaraf YG, et al. Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein. Blood. 2008;112(6):2489–99.

    Article  CAS  PubMed  Google Scholar 

  18. Richardson PG, Schlossman RL, Alsina M, et al. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013;122(14):2331–7.

    Article  CAS  PubMed  Google Scholar 

  19. Wang H, Baladandayuthapani V, Yan Lin H, et al. Mucin 20 (MUC20) Modulates Proteasome Assembly Chaperones through the c-MET Pathway and Is a Biomarker of Proteasome Inhibitor Sensitivity in Myeloma. Blood (ASH Annual Meeting Abstracts). 2014;124:274.

  20. Klimowicz A, Neri P, Belch A, et al. High Cereblon Protein Expression Correlates with Improved Response and Survival in Myeloma Patients Treated with Lenalidomide. Blood (ASH Annual Meeting Abstracts). 2012;120:931.

  21. Broyl A, Kuiper R, van Duin M, et al. Dutch-Belgian HOVON group; German GMMG Group. High cereblon expression is associated with better survival in patients with newly diagnosed multiple myeloma treated with thalidomide maintenance. Blood. 2013;121(4):624–7.

    Article  CAS  PubMed  Google Scholar 

  22. Heintel D, Rocci A, Ludwig H, et al. High expression of cereblon (CRBN) is associated with improved clinical response in patients with multiple myeloma treated with lenalidomide and dexamethasone. Br J Haematol. 2013;161(5):695–700.

    Article  CAS  PubMed  Google Scholar 

  23. Schuster SR, Kortuem KM, Zhu YX, et al. The clinical significance of cereblon expression in multiple myeloma. Leuk Res. 2014;38(1):23–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Gandhi AK, Mendy D, Waldman M, et al. Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity. Br J Haematol. 2014;164(2):233–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Maity R, Neri PE, Tagoug I, et al. Cereblon (CRBN) Splice Isoform Lacking Exon 10 Attenuates Lenalidomide-Mediated Degradation of Aiolos and Is Upregulated in Immunomodulatory Drugs (IMiDs) Resistant Myeloma (MM) Patients. Blood (ASH Annual Meeting Abstracts). 2014;124:639.

  26. Mateos MV, Martinez-Lopez J, Hernandez MT, et al. Comparison of Sequential Vs Alternating Administration of Bortezomib, Melphalan, Prednisone (VMP) and Lenalidomide Plus Dexamethasone (Rd) in Elderly Pts with Newly Diagnosed Multiple Myeloma (MM) Patients: GEM2010MAS65 Trial Blood (ASH Annual Meeting Abstracts). 2014;124:178.

Download references

Author information

Authors and Affiliations

  1. Department of Medicine I, Center for Oncology, Hematology and Outpatient Clinic and Palliative Care, Wilhelminenspital, 1160, Vienna, Montleartstr. 37, Austria

    Niklas Zojer

  2. C/o Department of Medicine I, Center for Oncology, Hematology and Outpatient Clinic and Palliative Care, Wilhelminen Cancer Research Institute, Wilhelminenspital, Vienna, Austria

    Heinz Ludwig

Authors
  1. Niklas Zojer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heinz Ludwig
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Niklas Zojer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zojer, N., Ludwig, H. Tailoring treatment in myeloma: are there clues from biology?. memo 8, 11–15 (2015). https://doi.org/10.1007/s12254-015-0207-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12254-015-0207-7

Keywords

Search

Navigation