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Multiple Myeloma, Gammopathies

Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma

Leukemia volume 30, pages 633–639 (2016)Cite this article

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Abstract

Early high-dose therapy (HDT), consisting of high-dose melphalan and autologous stem cell transplantation following doublet or triplet novel agent induction, is a preferred management strategy for transplant-eligible myeloma patients. We set out to examine the utility of the current fluorescence in situ hybridization (FISH)-based risk stratification in a homogenously treated population of transplant-eligible myeloma patients receiving novel induction regimens and early HDT with or without posttransplant maintenance therapy. FISH was available in 409 patients at the time of diagnosis for patients receiving HDT within 12 months of diagnosis. We present comprehensive outcomes for chromosome 14 translocations and 17p abnormalities that both support and refute current risk stratification models. In contrast to its current classification as a marker of 'standard risk' (SR), t(11;14) was associated with inferior overall survival (OS) when compared with the classical SR cohort. The use of novel agent maintenance therapy (bortezomib or lenalidomide) following early HDT ameliorates the negative prognostic value of high-risk (HR) cytogenetic markers. HR patients who received maintenance following early HDT had similar OS compared with the SR cohort at 5 years.

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References

  1. Boccadoro M, Cavallo F, Gay FM, Di Raimondo F, Nagler A, Montefusco V et al. Melphalan/prednisone/lenalidomide (MPR) versus high-dose melphalan and autologous transplantation (MEL200) plus lenalidomide maintenance or no maintenance in newly diagnosed multiple myeloma (MM) patients. J Clin Oncol 2013; Suppl (ASCO abstracts): abstract 8509.

  2. Palumbo A, Gay F, Spencer A, Di Raimondo F, Zdenek A, Larocca A et al. A phase III study of ASCT vs cyclophosphamide-lenalidomide-dexamethasone and lenalidomide-prednisone maintenance vs lenalidomide alone in newly diagnosed myeloma patients. Blood 2013; 122 (ASH abstracts): 763.

    Google Scholar 

  3. Moreau P, Attal M . All transplantation-eligible patients with myeloma should receive ASCT in first response. Hematology 2014; 2014: 250–254.

    Article  PubMed  Google Scholar 

  4. Rchardson PG, Laubach JP, Munshi NC, Anderson KC . Early or delayed transplantation for multiple myeloma in the era of novel therapy: does one size fit all? Hematology 2014; 2014: 255–261.

    Article  Google Scholar 

  5. Chng WJ, Dispenzieri A, Chim C-S, Fonseca R, Goldschmidt H, Lentzsch S et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia 2014; 28: 269–277.

    Article  CAS  PubMed  Google Scholar 

  6. Kapoor P, Fonseca R, Rajkumar SV, Sinha S, Gertz MA, Stewart AK et al. Evidence for cytogenetic and fluorescence in situ hybridization risk stratification of newly diagnosed multiple myeloma in the era of novel therapies. Mayo Clin Proc 2010; 85: 532–537.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Avet-Loiseau H. The future of FISH for the Diagnosis of Presenting Myeloma. EHA-SWG Scientific Meeting on Multiple Myeloma. September 2014. European Hematological Association: Barcelona, Spain, Abstract/Education book, pp 16–17.

  8. Kumar S, Fonseca R, Ketterling RP, Dispenzieri A, Lacy MQ, Gertz MA et al. Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics. Blood 2012; 119: 2100–2105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood 2007; 109: 3489–3495.

    Article  CAS  PubMed  Google Scholar 

  10. Gertz MA, Lacy MQ, Dispenzieri A, Greipp PR, Litzow MR, Henderson KJ et al. Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy. Blood 2005; 106: 2837–2840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chang H, Qi C, Yi QL, Reece D, Stewart AK . p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation. Blood 2005; 105: 358–360.

    Article  CAS  PubMed  Google Scholar 

  12. Drach J, Ackermann J, Fritz E, Krömer E, Schuster R, Gisslinger H et al. Presence of a p53 gene deletion in patients with multiple myeloma predicts for short survival after conventional-dose chemotherapy. Blood 1998; 92: 802–809.

    CAS  PubMed  Google Scholar 

  13. Fonseca R, Blood E, Rue M, Harrington D, Oken MM, Kyle RA et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood 2003; 101: 4569–4575.

    Article  CAS  PubMed  Google Scholar 

  14. Mikhael JR, Dingli D, Roy V, Reeder CB, Buadi FK, Hayman SR et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines 2013. Mayo Clin Proc 2013; 88: 360–376.

    Article  PubMed  Google Scholar 

  15. Moreau P, Attal M, Garban F, Hulin C, Facon T, Marit G et al. Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials. Leukemia 2007; 21: 2020–2024.

    Article  CAS  PubMed  Google Scholar 

  16. Sasaki K, Lu G, Saliba RM, Bashir Q, Hosing C, Popat U et al. Impact of t(11;14)(q13;q32) on the outcome of autologous hematopoietic cell transplantation in multiple myeloma. Biol Blood Marrow Transplant 2013; 19: 1227–1232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–1473.

    Article  CAS  PubMed  Google Scholar 

  18. Rajkumar SV . Multiple myeloma: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol 2014; 89: 999–1009.

    Article  Google Scholar 

  19. Soverini S, Cavo M, Cellini C, Terragna C, Zamagni E, Ruggeri D et al. Cyclin D1 overexpression is a favorable prognostic variable for newly diagnosed multiple myeloma patients treated with high-dose chemotherapy and single or double autologous transplantation. Blood 2003; 102: 1588–1594.

    Article  CAS  PubMed  Google Scholar 

  20. Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 2012; 366: 1782–1791.

    Article  CAS  PubMed  Google Scholar 

  21. McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012; 366: 1770–1781.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med 2014; 271: 895–905.

    Article  Google Scholar 

  23. Sonneveld P, Schmidt-Wolf IGH, van der Holt B, El Jarari L, Bertsch 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: 2946–2955.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    G P Kaufman, M A Gertz, A Dispenzieri, M Q Lacy, F K Buadi, D Dingli, S R Hayman, P Kapoor, J A Lust, S Russell, R S Go, Y L Hwa, R A Kyle, S V Rajkumar & S K Kumar

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  1. G P Kaufman
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  2. M A Gertz
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  3. A Dispenzieri
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  4. M Q Lacy
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  5. F K Buadi
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  6. D Dingli
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  7. S R Hayman
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  8. P Kapoor
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  9. J A Lust
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  10. S Russell
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  12. Y L Hwa
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  13. R A Kyle
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  14. S V Rajkumar
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  15. S K Kumar
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Correspondence to S K Kumar.

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Author contributions

GP Kaufman designed the research, collected and analyzed data and wrote the paper. SK Kumar designed the research, analyzed data and contributed to the writing of the paper. The other authors were involved in writing the manuscript.

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Kaufman, G., Gertz, M., Dispenzieri, A. et al. Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma. Leukemia 30, 633–639 (2016). https://doi.org/10.1038/leu.2015.287

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