Skip to main content
SpringerLink
Log in

Thrombosis events in Chinese patients with newly diagnosed multiple myeloma

  • Research
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

A high risk of thrombosis is seen in patients with newly diagnosed multiple myeloma (NDMM), particularly those treated with immunomodulatory drugs (IMiDs). Large cohorts addressing the thrombosis issue of NDMM patients in Asia are lacking. We retrospectively analyzed the clinical information of NDMM patients diagnosed in Zhongshan Hospital Fudan University, a national medical center, from January 2013 to June 2021. Death and thrombotic events (TEs) were the endpoints. To investigate risk factors for TEs, the Fine and Gray competing risk regression models were created, in which unrelated deaths were labeled as competing risk events. A total of 931 NDMM patients were recruited in our study. The median follow-up was 23 months [interquartile range (IQR): 9–43 months]. Forty-two patients (4.51%) developed TEs, including 40 cases (4.30%) of venous thrombosis and 2 cases (0.21%) of arterial thrombosis. The median time from taking first-line treatment to TEs occurrence was 2.03 months (IQR: 0.52–5.70 months). The cumulative incidence of TEs was higher in patients treated with IMiDs than in those without IMiDs (8.25 vs. 4.32%, p = 0.038). There was no difference in the incidence of TEs between lenalidomide-based and thalidomide-based groups (7.80 vs. 8.84%, p = 0.886). Besides, TEs occurrence did not adversely affect OS (p = 0.150) or PFS (p = 0.210) in MM patients. Chinese NDMM patients have a lower incidence of thrombosis than those in western countries. The risk of thrombosis was particularly increased in patients treated with IMiDs. TEs were not associated with inferior progression-free survival or overall survival.

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 that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

NDMM:

Newly diagnosed multiple myeloma

IMiDs:

Immunomodulatory drugs

TEs:

Thrombotic events

IQR:

Interquartile range

PFS:

Progression-free survival

OS:

Overall survival

MM:

Multiple myeloma

ATE:

Arterial thrombosis events

VTE:

Venous thrombosis events

MGUS:

Monoclonal gammopathy of uncertain significance

DVT:

Deep vein thrombosis

RRMM:

Relapsed and refractory multiple myeloma

IMWG:

International Myeloma Working Group

BMI:

Body mass index

LDH:

Lactate dehydrogenase

IFE:

Immunofixation electrophoresis

ECOG:

Eastern Cooperative Oncology Group

ISS:

International Staging System

RISS:

Revised International Staging System

FISH:

Fluorescent in situ hybridization

EPO:

Use of erythropoietin

CVC:

Central venous catheterization

PE:

Pulmonary embolism

SHR:

Subdistribution hazard ratios

HR:

Hazard ratio

CI:

Confidence interval

DOAC(s):

Direct oral anticoagulant(s)

LMWH:

Low-molecular-weight heparin

References

  1. Falanga A, Marchetti M. Venous thromboembolism in the hematologic malignancies. J Clin Oncol. 2009;27(29):4848–57. https://doi.org/10.1200/jco.2009.22.8197.

    Article  CAS  PubMed  Google Scholar 

  2. Kristinsson SY, Pfeiffer RM, Björkholm M, et al. Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study. Blood. 2010;115(24):4991–8. https://doi.org/10.1182/blood-2009-11-252072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22(2):414–23. https://doi.org/10.1038/sj.leu.2405062.

    Article  CAS  PubMed  Google Scholar 

  4. Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5(3):632–4. https://doi.org/10.1111/j.1538-7836.2007.02374.x.

    Article  CAS  PubMed  Google Scholar 

  5. Kristinsson SY, Fears TR, Gridley G, et al. Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma. Blood. 2008;112(9):3582–6. https://doi.org/10.1182/blood-2008-04-151076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Swan D, Rocci A, Bradbury C, Thachil J. Venous thromboembolism in multiple myeloma - choice of prophylaxis, role of direct oral anticoagulants and special considerations. Br J Haematol. 2018;183(4):538–56. https://doi.org/10.1111/bjh.15684.

    Article  PubMed  Google Scholar 

  7. Dimopoulos MA, Zervas K, Kouvatseas G, et al. Thalidomide and dexamethasone combination for refractory multiple myeloma. Ann Oncol. 2001;12(7):991–5. https://doi.org/10.1023/a:1011132808904.

    Article  CAS  PubMed  Google Scholar 

  8. Dimopoulos MA, Chen C, Spencer A, et al. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009;23(11):2147–52. https://doi.org/10.1038/leu.2009.147.

    Article  CAS  PubMed  Google Scholar 

  9. Bradbury CA, Craig Z, Cook G, et al. Thrombosis in patients with myeloma treated in the Myeloma IX and Myeloma XI phase 3 randomized controlled trials. Blood. 2020;136(9):1091–104. https://doi.org/10.1182/blood.2020005125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Li A, Wu Q, Warnick G, et al. The incidence of thromboembolism for lenalidomide versus thalidomide in older patients with newly diagnosed multiple myeloma. Ann Hematol. 2020;99(1):121–6. https://doi.org/10.1007/s00277-019-03860-2.

    Article  PubMed  Google Scholar 

  11. Li W, Garcia D, Cornell RF, et al. Cardiovascular and thrombotic complications of novel multiple myeloma therapies: a review. JAMA Oncol. 2017;3(7):980–8. https://doi.org/10.1001/jamaoncol.2016.3350.

    Article  PubMed  Google Scholar 

  12. Km M, Fs D, Ai S, At T. Incidence and prophylaxis of venous thromboembolic events in multiple myeloma patients receiving immunomodulatory therapy. Thrombosis Res: Int J Vasc Obstr, Hemorrhage Hemost. 2009;123(5):679–86.

    Article  Google Scholar 

  13. Roberts LN, Patel RK, Arya R. Venous thromboembolism and ethnicity. Br J Haematol. 2009;146(4):369–83. https://doi.org/10.1111/j.1365-2141.2009.07786.x.

    Article  PubMed  Google Scholar 

  14. Shyu BH, Wang PN, Chu PH. Low incidence of venous thromboembolism in Asian myeloma patients treated with thalidomide plus dexamethasone. Asia-Pacific J Oncol Hematol. 2010;2(1):41–7.

    Google Scholar 

  15. Hou J, Du X, Jin J, et al. A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial. J Hematol Oncol. 2013;6:41. https://doi.org/10.1186/1756-8722-6-41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gu Y, Chen LJ, Qu XY, et al. Clinical analysis of thromboembolism associated with lenalidomide-based regimens for multiple myeloma patients. Zhonghua Xue Ye Xue Za Zhi. 2016;37(3):245–7. https://doi.org/10.3760/cma.j.issn.0253-2727.2016.03.015.

    Article  CAS  PubMed  Google Scholar 

  17. Sanfilippo KM, Luo S, Wang TF, et al. Predicting venous thromboembolism in multiple myeloma: development and validation of the IMPEDE VTE score. Am J Hematol. 2019;94(11):1176–84. https://doi.org/10.1002/ajh.25603.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Li A, Wu Q, Luo S, et al. Derivation and validation of a risk assessment model for immunomodulatory drug-associated thrombosis among patients with multiple myeloma. J Natl Compr Canc Netw. 2019;17(7):840–7. https://doi.org/10.6004/jnccn.2018.7273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Covut F, Ahmed R, Chawla S, et al. Validation of the IMPEDE VTE score for prediction of venous thromboembolism in multiple myeloma: a retrospective cohort study. Br J Haematol. 2021;193(6):1213–9. https://doi.org/10.1111/bjh.17505.

    Article  CAS  PubMed  Google Scholar 

  20. Koh Y, Bang SM, Lee JH, et al. Low incidence of clinically apparent thromboembolism in Korean patients with multiple myeloma treated with thalidomide. Ann Hematol. 2010;89(2):201–6. https://doi.org/10.1007/s00277-009-0807-6.

    Article  CAS  PubMed  Google Scholar 

  21. 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. https://doi.org/10.1016/s1470-2045(14)70442-5.

    Article  PubMed  Google Scholar 

  22. 2003 Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 121(5): 749 757 https://doi.org/10.1046/j.1365-2141.2003.04355.x

  23. Carrier M, Khorana AA, Zwicker JI, Lyman GH, Le Gal G, Lee AY. Venous thromboembolism in cancer clinical trials: recommendation for standardized reporting and analysis. J Thromb Haemost. 2012;10(12):2599–601. https://doi.org/10.1111/jth.12028.

    Article  CAS  PubMed  Google Scholar 

  24. Chalayer E, Talbot A, Frenzel L, et al. Prediction of venous thromboembolism in patients with multiple myeloma treated with lenalidomide, bortezomib, dexamethasone, and transplantation: Lessons from the substudy of IFM/DFCI 2009 cohort. J Thromb Haemost. 2022;20(8):1859–67. https://doi.org/10.1111/jth.15758.

    Article  CAS  PubMed  Google Scholar 

  25. Fotiou D, Gavriatopoulou M, Terpos E. Multiple myeloma and thrombosis: prophylaxis and risk prediction tools. Cancers (Basel). 2020;12(1):191. https://doi.org/10.3390/cancers12010191.

    Article  CAS  PubMed  Google Scholar 

  26. Leclerc V, Karlin L, Herledan C, et al. Thromboembolic events and thromboprophylaxis associated with immunomodulators in multiple myeloma patients: a real-life study. J Cancer Res Clin Oncol. 2022;148(4):975–84. https://doi.org/10.1007/s00432-021-03693-5.

    Article  CAS  PubMed  Google Scholar 

  27. Knight R, DeLap RJ, Zeldis JB. Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med. 2006;354(19):2079–80. https://doi.org/10.1056/NEJMc053530.

    Article  CAS  PubMed  Google Scholar 

  28. Kato A, Takano H, Ichikawa A, et al. A retrospective cohort study of venous thromboembolism(VTE) in 1035 Japanese myeloma patients treated with thalidomide; lower incidence without statistically significant association between specific risk factors and development of VTE and effects of thromboprophylaxis with aspirin and warfarin. Thromb Res. 2013;131(2):140–4. https://doi.org/10.1016/j.thromres.2012.11.014.

    Article  CAS  PubMed  Google Scholar 

  29. Gay F, Hayman SR, Lacy MQ, et al. Lenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma: a comparative analysis of 411 patients. Blood. 2010;115(7):1343–50. https://doi.org/10.1182/blood-2009-08-239046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kristinsson SY, Pfeiffer RM, Björkholm M, Schulman S, Landgren O. Thrombosis is associated with inferior survival in multiple myeloma. Haematologica. 2012;97(10):1603–7. https://doi.org/10.3324/haematol.2012.064444.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Anaissie EJ, Coleman EA, Goodwin JA, et al. Prophylactic recombinant erythropoietin therapy and thalidomide are predictors of venous thromboembolism in patients with multiple myeloma: limited effectiveness of thromboprophylaxis. Cancer. 2012;118(2):549–57. https://doi.org/10.1002/cncr.26302.

    Article  CAS  PubMed  Google Scholar 

  32. Carrier M, Le Gal G, Tay J, Wu C, Lee AY. Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta-analysis. J Thromb Haemost. 2011;9(4):653–63. https://doi.org/10.1111/j.1538-7836.2011.04215.x.

    Article  CAS  PubMed  Google Scholar 

  33. Cornell RF, Goldhaber SZ, Engelhardt BG, et al. Primary prevention of venous thromboembolism with apixaban for multiple myeloma patients receiving immunomodulatory agents. Br J Haematol. 2020;190(4):555–61. https://doi.org/10.1111/bjh.16653.

    Article  CAS  PubMed  Google Scholar 

  34. Zangari M, Anaissie E, Barlogie B, et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood. 2001;98(5):1614–5. https://doi.org/10.1182/blood.v98.5.1614.

    Article  CAS  PubMed  Google Scholar 

  35. Leleu X, Rodon P, Hulin C, et al. MELISSE, a large multicentric observational study to determine risk factors of venous thromboembolism in patients with multiple myeloma treated with immunomodulatory drugs. Thromb Haemost. 2013;110(4):844–51. https://doi.org/10.1160/th13-02-0140.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank all collaborators of the study.

Funding

This work was supported by the National Science Foundation of China under Grant 82100215, Programs of Introduction of Talents for Key Positions by Fudan University in 2014, Science Foundation of Shanghai under Grant 22ZR1411400.

Author information

Author notes

  1. Panpan Li, Bei Xu, Jiadai Xu, and Yawen Wang contributed equally to this study.

Authors and Affiliations

  1. Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China

    Panpan Li, Bei Xu, Jiadai Xu, Yawen Wang, Yang Yang, Wenjing Wang, Aiziguli Maihemaiti, Jing Li, Tianhong Xu, Liang Ren, Tianwei Lan, Chi Zhou, Pu Wang & Peng Liu

  2. Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China

    Panpan Li, Bei Xu, Jiadai Xu, Yawen Wang, Yang Yang, Wenjing Wang, Aiziguli Maihemaiti, Jing Li, Tianhong Xu, Liang Ren, Tianwei Lan, Chi Zhou, Pu Wang & Peng Liu

  3. Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China

    Bei Xu

Authors
  1. Panpan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bei Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiadai Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yawen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenjing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aiziguli Maihemaiti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tianhong Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Liang Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Tianwei Lan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Chi Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Pu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Peng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Peng Liu designed the study and approved the final version. Panpan Li was responsible for data collection, literature research, statistical analysis, and manuscript writing. Bei Xu, Jiadai Xu, and Yawen Wang were responsible for data review, statistical analysis plan development, and manuscript revision. All authors revised the results and approved the final version of the manuscript.

Corresponding author

Correspondence to Peng Liu.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 174 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, P., Xu, B., Xu, J. et al. Thrombosis events in Chinese patients with newly diagnosed multiple myeloma. Clin Exp Med 23, 3809–3820 (2023). https://doi.org/10.1007/s10238-023-01080-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-023-01080-7

Keywords

Search

Navigation