Skip to main content
SpringerLink
Log in

Outcomes of patients with multiple myeloma harboring chromosome 1q gain/amplification in the era of modern therapy

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

Abstract

Chromosome 1q gain/amplification (1q +) has been reported to be associated with inferior outcomes in multiple myeloma (MM) patients. Big therapeutic advances have shifted the treatment landscape by introducing monoclonal antibodies. There is a relative lack of data on outcomes in patients harboring this alteration in the era of monoclonal antibodies. Baseline characteristics and therapy-related data from newly diagnosed MM patients harboring 1q + detected by fluorescence in situ hybridization (FISH) were collected in a single institution. Among 34 identified subjects, the presence of elevated LDH was found to be associated with shorter overall survival (OS), and increased bone marrow plasma cell percentage (≥ 60%) was associated with worse progression-free survival (PFS). 1q + copy number more than three was associated with both shorter OS and PFS. Additionally, the administration of lenalidomide was associated with superior OS. The use of autologous stem cell transplantation, bortezomib, or daratumumab, was found to have no prognostic benefits in our sample. Lenalidomide may be an optimal therapeutic choice for this population, and future larger studies are warranted to confirm this benefit and further investigate the role of monoclonal antibodies in this subpopulation.

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
Fig. 3

Similar content being viewed by others

Data availability

The data of this study are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

References

  1. Kazandjian D (2016) Multiple myeloma epidemiology and survival: a unique malignancy. Semin Oncol 43(6):676–681

    Article  PubMed  PubMed Central  Google Scholar 

  2. National Cancer Institute S, Epidemiology, and End Results Program (2021) (Cited 2021 September 5). Cancer Stat facts: myleoma. Available from: https://seer.cancer.gov/statfacts/html/mulmy.html

  3. Palumbo A, Anderson K (2011) Multiple myeloma. N Engl J Med 364(11):1046–1060

    Article  CAS  PubMed  Google Scholar 

  4. Kristinsson SY, Anderson WF, Landgren O (2014) Improved long-term survival in multiple myeloma up to the age of 80 years. Leukemia 28(6):1346–1348

    Article  CAS  PubMed  Google Scholar 

  5. Bergsagel PL, Mateos MV, Gutierrez NC, Rajkumar SV, San Miguel JF (2013) Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma. Blood 121(6):884–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L et al (2015) Revised international staging system for multiple myeloma: a report from international myeloma working group. J Clin Oncol 33(26):2863–2869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Walker BA, Leone PE, Chiecchio L, Dickens NJ, Jenner MW, Boyd KD et al (2010) A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value. Blood 116(15):e56-65

    Article  CAS  PubMed  Google Scholar 

  8. Saxe D, Seo EJ, Bergeron MB, Han JY (2019) Recent advances in cytogenetic characterization of multiple myeloma. Int J Lab Hematol 41(1):5–14

    Article  PubMed  Google Scholar 

  9. Dewald GW, Kyle RA, Hicks GA, Greipp PR (1985) The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis. Blood 66(2):380–390

    Article  CAS  PubMed  Google Scholar 

  10. Ganoth D, Bornstein G, Ko TK, Larsen B, Tyers M, Pagano M et al (2001) The cell-cycle regulatory protein Cks1 is required for SCF(Skp2)-mediated ubiquitinylation of p27. Nat Cell Biol 3(3):321–324

    Article  CAS  PubMed  Google Scholar 

  11. Spruck C, Strohmaier H, Watson M, Smith APL, Ryan A, Krek W et al (2001) A CDK-independent function of mammalian Cks1. Mol Cell 7(3):639–650

    Article  CAS  PubMed  Google Scholar 

  12. Avet-Loiseau H, Attal M, Campion L, Caillot D, Hulin C, Marit G et al (2012) Long-term analysis of the IFM 99 trials for myeloma: cytogenetic abnormalities [t(4;14), del(17p), 1q gains] play a major role in defining long-term survival. J Clin Oncol 30(16):1949–1952

    Article  PubMed  Google Scholar 

  13. Schmidt TM, Barwick BG, Joseph N, Heffner LT, Hofmeister CC, Bernal L et al (2019) Gain of Chromosome 1q is associated with early progression in multiple myeloma patients treated with lenalidomide, bortezomib, and dexamethasone. Blood Cancer J 9(12):94

    Article  PubMed  PubMed Central  Google Scholar 

  14. Shah GL, Landau H, Londono D, Devlin SM, Kosuri S, Lesokhin AM et al (2017) Gain of chromosome 1q portends worse prognosis in multiple myeloma despite novel agent-based induction regimens and autologous transplantation. Leuk Lymphoma 58(8):1823–1831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rajkumar SV, Kumar S (2016) Multiple myeloma: diagnosis and treatment. Mayo Clin Proc 91(1):101–119

    Article  PubMed  Google Scholar 

  16. Abdallah N, Greipp P, Kapoor P, Gertz MA, Dispenzieri A, Baughn LB et al (2020) Clinical characteristics and treatment outcomes of newly diagnosed multiple myeloma with chromosome 1q abnormalities. Blood Adv 4(15):3509–3519

    Article  PubMed  PubMed Central  Google Scholar 

  17. Leone PE, Walker BA, Jenner MW, Chiecchio L, Dagrada G, Protheroe RK et al (2008) Deletions of CDKN2C in multiple myeloma: biological and clinical implications. Clin Cancer Res 14(19):6033–6041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hebraud B, Leleu X, Lauwers-Cances V, Roussel M, Caillot D, Marit G et al (2014) Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients. Leukemia 28(3):675–679

    Article  CAS  PubMed  Google Scholar 

  19. Boyd KD, Ross FM, Walker BA, Wardell CP, Tapper WJ, Chiecchio L, et al. Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as being genes in regions associated with adverse survival. Clin Cancer Res. 2011;17(24):7776–84.

  20. Varma A, Sui D, Milton DR, Tang G, Saini N, Hasan O et al (2020) Outcome of multiple myeloma with chromosome 1q gain and 1p deletion after autologous hematopoietic stem cell transplantation: propensity score matched analysis. Biol Blood Marrow Transplant 26(4):665–671

    Article  PubMed  Google Scholar 

  21. Chen D, Zhou D, Xu J, Zhou R, Ouyang J, Chen B (2019) Prognostic value of 1q21 gain in multiple myeloma. Clin Lymphoma Myeloma Leuk 19(3):e159–e164

    Article  PubMed  Google Scholar 

  22. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos M-V et al (2014) International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15(12):e538–e548

    Article  PubMed  Google Scholar 

  23. An G, Li Z, Tai YT, Acharya C, Li Q, Qin X et al (2015) The impact of clone size on the prognostic value of chromosome aberrations by fluorescence in situ hybridization in multiple myeloma. Clin Cancer Res 21(9):2148–2156

    Article  PubMed  Google Scholar 

  24. Ross FM, Avet-Loiseau H, Ameye G, Gutierrez 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  PubMed Central  Google Scholar 

  25. Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P et al (2016) International myeloma working group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 17(8):e328–e346

    Article  PubMed  Google Scholar 

  26. Du C, Mao X, Xu Y, Yan Y, Yuan C, Du X et al (2020) 1q21 gain but not t(4;14) indicates inferior outcomes in multiple myeloma treated with bortezomib. Leuk Lymphoma 61(5):1201–1210

    Article  CAS  PubMed  Google Scholar 

  27. Terpos E, Katodritou E, Roussou M, Pouli A, Michalis E, Delimpasi S et al (2010) High serum lactate dehydrogenase adds prognostic value to the international myeloma staging system even in the era of novel agents. Eur J Haematol 85(2):114–119

    PubMed  Google Scholar 

  28. 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 

  29. Al Saleh AS, Parmar HV, Visram A, Muchtar E, Buadi FK, Go RS et al (2020) Increased bone marrow plasma-cell percentage predicts outcomes in newly diagnosed multiple myeloma patients. Clin Lymphoma Myeloma Leuk 20(9):596–601

    Article  PubMed  PubMed Central  Google Scholar 

  30. Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B et al (2012) Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood 119(4):940–948

    Article  CAS  PubMed  Google Scholar 

  31. 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 tandem stem-cell transplantation. Blood 108(5):1724–1732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. An G, Xu Y, Shi L, Shizhen Z, Deng S, Xie Z et al (2014) Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value. Haematologica 99(2):353–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Qu X, Chen L, Qiu H, Lu H, Wu H, Qiu H, et al. Extramedullary manifestation in multiple myeloma bears high incidence of poor cytogenetic aberration and novel agents resistance. Biomed Res Int. 2015;2015:787809.

  34. Usmani SZ, Heuck C, Mitchell A, Szymonifka J, Nair B, Hoering A et al (2012) Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents. Haematologica 97(11):1761–1767

    Article  PubMed  PubMed Central  Google Scholar 

  35. Landau H, Pandit-Taskar N, Hassoun H, Cohen A, Lesokhin A, Lendvai N et al (2012) Bortezomib, liposomal doxorubicin and dexamethasone followed by thalidomide and dexamethasone is an effective treatment for patients with newly diagnosed multiple myeloma with Internatinal Staging System stage II or III, or extramedullary disease. Leuk Lymphoma 53(2):275–281

    Article  CAS  PubMed  Google Scholar 

  36. Shah V, Sherborne AL, Walker BA, Johnson DC, Boyle EM, Ellis S et al (2018) Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles of 1905 trial patients. Leukemia 32(1):102–110

    Article  CAS  PubMed  Google Scholar 

  37. Shaughnessy JD Jr, Qu P, Usmani S, Heuck CJ, Zhang Q, Zhou Y et al (2011) Pharmacogenomics of bortezomib test-dosing identifies hyperexpression of proteasome genes, especially PSMD4, as novel high-risk feature in myeloma treated with Total Therapy 3. Blood 118(13):3512–3524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Scott EC, Hari P, Sharma M, Le-Rademacher J, Huang J, Vogl D et al (2016) Post-transplant outcomes in high-risk compared with non-high-risk multiple myeloma: a CIBMTR analysis. Biol Blood Marrow Transplant 22(10):1893–1899

    Article  PubMed  PubMed Central  Google Scholar 

  39. Chari A, Suvannasankha A, Fay JW, Arnulf B, Kaufman JL, Ifthikharuddin JJ et al (2017) Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood 130(8):974–981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Usmani SZ, Weiss BM, Plesner T, Bahlis NJ, Belch A, Lonial S et al (2016) Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood 128(1):37–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mateos MV, Spencer A, Nooka AK, Pour L, Weisel K, Cavo M et al (2020) Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies. Haematologica 105(2):468–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N et al (2019) Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med 380(22):2104–2115

    Article  CAS  PubMed  Google Scholar 

  43. Giri S, Grimshaw A, Bal S, Godby K, Kharel P, Djulbegovic B, et al. Evaluation of daratumumab for the treatment of multiple myeloma in patients with high-risk cytogenetic factors: a systematic review and meta-analysis. JAMA Oncol. 2020.

  44. Mohan M, Weinhold N, Schinke C, Thanedrarajan S, Rasche L, Sawyer JR et al (2020) Daratumumab in high-risk relapsed/refractory multiple myeloma patients: adverse effect of chromosome 1q21 gain/amplification and GEP70 status on outcome. Br J Haematol 189(1):67–71

    Article  CAS  PubMed  Google Scholar 

  45. Paul Richardson SH, Thierry Facon, Kwee Yong. Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with 1q21 gain: insights from phase 1 and phase 3 studies. Abstract and Poster EP1017 EHA 2020 June 12, 2020.

  46. Schmidt TM, Fonseca R, Usmani SZ (2021) Chromosome 1q21 abnormalities in multiple myeloma. Blood Cancer J 11(4):83

    Article  PubMed  PubMed Central  Google Scholar 

  47. Ogiya D, Liu J, Ohguchi H, Kurata K, Samur MK, Tai YT et al (2020) The JAK-STAT pathway regulates CD38 on myeloma cells in the bone marrow microenvironment: therapeutic implications. Blood 136(20):2334–2345

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Thanks to the staff of the Cytogenetics Laboratory at Tufts Medical Center for their contributions to this work.

Author information

Authors and Affiliations

  1. Division of Hematology-Oncology, Tufts Medical Center, Boston, MA, 02111, USA

    Xiao Hu, Raymond L. Comenzo & Cindy Varga

  2. Department of Medicine, Tufts Medical Center, Boston, MA, 02111, USA

    Cherng-Horng Wu

  3. Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, 02111, USA

    Janet M. Cowan

  4. Tufts Medical Center, The John Conant Davis Myeloma and Amyloid Program, Boston, MA, 02111, USA

    Raymond L. Comenzo & Cindy Varga

Authors
  1. Xiao Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cherng-Horng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Janet M. Cowan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Raymond L. Comenzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cindy Varga
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Xiao Hu, Cherng-Horng Wu, Janet M. Cowan, and Cindy Varga. First draft of the manuscript was written by Xiao Hu, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Cindy Varga.

Ethics declarations

Ethics approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. The respective Institutional Review Boards at Tufts Medical Center approved this study. As this was a retrospective study, informed consent could not be obtained from all patients included in the study.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Conflict of interest/Competing interests

All authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, X., Wu, CH., Cowan, J.M. et al. Outcomes of patients with multiple myeloma harboring chromosome 1q gain/amplification in the era of modern therapy. Ann Hematol 101, 369–378 (2022). https://doi.org/10.1007/s00277-021-04704-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-021-04704-8

Keywords

Search

Navigation