Evaluation of thrombosis-related biomarkers before and after therapy in patients with multiple myeloma

Abstract

Background

Thrombosis is one of the complications in the clinical course of multiple myeloma (MM). Vascular endothelial cells and/or the hemostatic-coagulatory system are thought to play an important role in thrombosis of MM. In addition to melphalan-prednisone (Mel-P) therapy, several new therapeutic drugs such as lenalidomide or bortezomib have been developed and show effectiveness against MM. However, these new drugs also have risk of therapy-related thrombosis.

Methods

We assessed 103 MM patients and 30 healthy controls, using enzyme-linked immunosorbent assays to evaluate five biomarkers: platelet-derived microparticles (PDMP), plasminogen activator inhibitor-1 (PAI-1), high mobility group box protein-1 (HMGB1), endothelial protein C receptor (EPCR), and soluble vascular cell adhesion molecule-1 (sVCAM-1). The effects of Mel-P, bortezomib, and lenalidomide on the plasma concentrations of these biomarkers were investigated.

Results

The plasma concentrations of PDMP, PAI-1, HMGB1, EPCR, and sVCAM-1 were higher in MM patients than in healthy controls. Mel-P, bortezomib, and lenalidomide therapies all reduced biomarker levels after treatment. However, when only patients with higher levels of EPCR were compared, differences were seen between the three therapies in the elevation of PDMP, HMGB1, and PAI-1.

Conclusion

These results suggest that both MM and therapies for MM can induce a hypercoagulable state. The elevated risk of thrombosis conferred by hypercoagulability increases patient morbidity and mortality. Attention should be paid to therapy-related thrombosis when new therapeutic regimens are selected for MM patients.

Keywords:

• multiple myeloma
• bortezomib
• lenaridomide
• thrombosis
• biomarker

Acknowledgments

The authors thank Dr Akiko Konishi, Dr Yukie Tsubokura, and Dr Yoshiko Azuma for technical assistance and for data collection. This study was supported in part by a grant from the Japan Foundation of Neuropsychiatry and Hematology Research, the Research Grant for Advanced Medical Care from the Ministry of Health and Welfare of Japan, and a grant (13670760 to SN) from the Ministry of Education, Science and Culture of Japan.

The abstract of this paper was presented as a poster presentation with interim findings at the 2017 Annual Meeting of the International Society for Laboratory Hematology, 4–6 May 2017, Honolulu, HI, USA, and was published in the International Journal of Laboratory Hematology, Volume 39, Issue S2 May 2017. The poster’s abstract was published in “Poster Abstracts” in the International Journal of Laboratory Hematology: http://onlinelibrary.wiley.com/doi/10.1111/ijlh.2017.39.issue-S2/issuetoc.

Author contributions

All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.