Skip to main content
SpringerLink
Log in

Clinical and prognostic significance of t(4;14) translocation in multiple myeloma in the era of novel agents

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

Abstract

Translocation t(4;14) is an independent prognostic factor for adverse outcome in multiple myeloma (MM). However, reports concerning the therapeutic effects of novel drugs on t(4;14) MM are few. We retrospectively investigated the clinical and prognostic significance of symptomatic MM cases with t(4;14) treated with novel therapies. Ninety-three patients (IgG, 56; IgA, 23; BjP, 14) newly diagnosed with MM were included (median age, 71 years; median observation period, 27.8 months). t(4;14) MM was diagnosed in 17 (IgG, 7; IgA, 9; BjP, 1) patients (18%). An association between t(4;14) and the IgA isotype was confirmed (p = 0.02). Overall survival (OS) at 3 years was lower in the t(4;14) patients than without t(4;14) group (81.2% vs 66.7%, p = 0.04). Multivariate analysis showed that t(4;14) was an independent predictor of OS (hazard ratio [HR], 7.58; 95.0% confidence interval [CI], 1.43–39.9; p = 0.0017). The ORR after autologous blood stem cell transplantation (ASCT) did not differ with or without t(4;14); progression-free survival tended to be prolonged in the group without t(4;14) (p = 0.088). Thus, even in the era of novel drugs, t(4;14) MM still has a poor prognosis, and triplet consolidation therapy should be continued.

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

Similar content being viewed by others

References

  1. Fonseca R, Barlogie B, Bataille R, Bastard C, Bergsagel PL, Chesi M, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 2004;64:1546–58.

    Article  CAS  Google Scholar 

  2. Gonzalez D, van der Burg M, Garcia-Sanz R, Fenton JA, Langerak AW, Gonzalez M, et al. Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma. Blood. 2007;110:3112–211.

    Article  CAS  Google Scholar 

  3. Kumar S, Zhang L, Dispenzieri A, Van Wier S, Katzmann JA, Snyder M, et al. Relationship between elevated immunoglobulin free light chain and presence of IgH translocations in multiple myeloma. Leukemia. 2010;24:1498–505.

    Article  CAS  Google Scholar 

  4. Kuehl WM, Bergasagel PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer. 2002;2:175–87.

    Article  CAS  Google Scholar 

  5. Chesi M, Nardini E, Lim RS, Smith KD, Kuehl WM, Bergsagel PL. The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts. Blood. 1998;92:3025–34.

    Article  CAS  Google Scholar 

  6. Santra M, Zhan F, Tian E, Barlogie B, Shaughnessy J Jr. A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript. Blood. 2003;101:2374–6.

    Article  CAS  Google Scholar 

  7. Chang H, Stewart AK, Qi XY, Li ZH, Yi QL, Trudel S. Immunohistochemistry accurately predicts FGFR3 aberrant expression and t(4;14) in multiple myeloma. Blood. 2005;106:353–5.

    Article  CAS  Google Scholar 

  8. Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Foldschmidt H, Rosinol L, et al. Revised international staging system for multiple myeloma: a report from international myeloma working group. J Clin Oncol. 2015;33:2863–9.

    Article  CAS  Google Scholar 

  9. Chang H, Sloan S, Li D, Zhuang L, Yi QL, Chen CI, et al. The t(4;14) is associated with poor prognosis in myeloma patients undergoing autologous stem cell transplant. Br J Haematol. 2004;125:64–8.

    Article  Google Scholar 

  10. Sonneveld P, Schmidt-Wolf IG, van der Holt B, el Jarari L, Bretsch U, Salwender H, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial. J Clin Oncol. 2012;30:2946–55.

    Article  CAS  Google Scholar 

  11. Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, et al. 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 randomized phase 3 study. Lancet. 2010;376:2075–85.

    Article  CAS  Google Scholar 

  12. Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380:2104–15.

    Article  CAS  Google Scholar 

  13. 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–e548548.

    Article  Google Scholar 

  14. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    Article  CAS  Google Scholar 

  15. Moreau P, Facon T, Leleu X, Morineau N, Huyghe P, Harousseau JL, et al. Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy. Blood. 2002;100:1579–83.

    Article  CAS  Google Scholar 

  16. Morie AG, Martha QL, Angela D, Greipp PR, Litzow MR, Henderson KJ, et al. Clinical implications of t(11;14)(q13;32), t(4;14)(p16.3;q32), and − 17p13 in myeloma patients treated with high-dose therapy. Blood. 2005;106:2837–40.

    Google Scholar 

  17. Durie BG, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389:519–27.

    Article  CAS  Google Scholar 

  18. Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, et al. Treatment with carfilzomib–lenalidomide–dexamethasone with lenalidomide extension in patients with smoldering or newly diagnosed multiple myeloma. JAMA Oncol. 2015;1:746–54.

    Article  Google Scholar 

  19. Rawstron AC, Child JA, de Tute RM, Davies FE, Gregory WM, Bell SE, et al. Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: impact on outcome in the Medical Research Council Myeloma IX Study. J Clin Oncol. 2013;31:2540–7.

    Article  Google Scholar 

  20. Yan X, Clemens PL, Puchalski T, Lonial S, Lokhorst H, Moorhees PM, et al. Influence of disease and patient characteristics on daratumumab exposure and clinical outcomes in relapsed or refractory multiple myeloma. Clin Pharmacokinet. 2018;57:529–38.

    Article  CAS  Google Scholar 

  21. Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 2007;7:715–25.

    Article  CAS  Google Scholar 

  22. Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319–31.

    Article  CAS  Google Scholar 

  23. Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Baksac M, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:754–66.

    Article  CAS  Google Scholar 

  24. Mateos MV, Dimopoulous MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, et al. Daratumimab plus bortezomib, melphalan, and predonisone for untreated myeloma. N Engl J Med. 2018;378:518–28.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura, Kanagawa, 247-0072, Japan

    Shuku Sato, Wataru Kamata, Satomi Okada & Yotaro Tamai

  2. Division of Hematology, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura, Kanagawa, 247-8533, Japan

    Shuku Sato

Authors
  1. Shuku Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wataru Kamata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Satomi Okada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yotaro Tamai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shuku Sato.

Ethics declarations

Conflict of interest

The authors declare that 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.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sato, S., Kamata, W., Okada, S. et al. Clinical and prognostic significance of t(4;14) translocation in multiple myeloma in the era of novel agents. Int J Hematol 113, 207–213 (2021). https://doi.org/10.1007/s12185-020-03005-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-020-03005-6

Keywords

Search

Navigation