Endothelial stress products and coagulation markers in patients with multiple myeloma treated with lenalidomide plus dexamethasone: an observational study

Authors

  • Rachel Rosovsky,

    Corresponding author
    1. Harvard Medical School, Boston, MA, USA
    • Medical Oncology, Massachusetts General Hospital, Boston, MA, USA
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  • Fangxin Hong,

    1. Harvard Medical School, Boston, MA, USA
    2. Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA
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  • Deanna Tocco,

    1. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Dana–Farber Cancer Institute, Boston, MA, USA
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  • Brendan Connell,

    1. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Dana–Farber Cancer Institute, Boston, MA, USA
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  • Constantine Mitsiades,

    1. Harvard Medical School, Boston, MA, USA
    2. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Dana–Farber Cancer Institute, Boston, MA, USA
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  • Robert Schlossman,

    1. Harvard Medical School, Boston, MA, USA
    2. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Dana–Farber Cancer Institute, Boston, MA, USA
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  • Irene Ghobrial,

    1. Harvard Medical School, Boston, MA, USA
    2. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Dana–Farber Cancer Institute, Boston, MA, USA
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  • Leslie Lockridge,

    1. Harvard Medical School, Boston, MA, USA
    2. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Dana–Farber Cancer Institute, Boston, MA, USA
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  • Diane Warren,

    1. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Dana–Farber Cancer Institute, Boston, MA, USA
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  • Gary Bradwin,

    1. Harvard Medical School, Boston, MA, USA
    2. Laboratory Medicine, Children's Hospital, Boston, MA, USA
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  • Mary Doyle,

    1. Instrumentation Laboratory, Lexington, MA, USA
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  • Nikhil Munshi,

    1. Harvard Medical School, Boston, MA, USA
    2. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Dana–Farber Cancer Institute, Boston, MA, USA
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  • Robert J. Soiffer,

    1. Harvard Medical School, Boston, MA, USA
    2. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Dana–Farber Cancer Institute, Boston, MA, USA
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  • Kenneth C. Anderson,

    1. Harvard Medical School, Boston, MA, USA
    2. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Dana–Farber Cancer Institute, Boston, MA, USA
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  • Edie Weller,

    1. Harvard Medical School, Boston, MA, USA
    2. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Dana–Farber Cancer Institute, Boston, MA, USA
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  • Paul Richardson

    1. Harvard Medical School, Boston, MA, USA
    2. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Dana–Farber Cancer Institute, Boston, MA, USA
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Correspondence: Rachel Rosovsky, Massachusetts General Hospital, POB 246, 55 Fruit Street, Boston, MA 02114, USA.

E-mail: rprosovsky@partners.org

Summary

In this prospective study of patients with relapsed or relapsed and refractory multiple myeloma (MM) treated with lenalidomide and dexamethasone, relationships between markers of endothelial stress and drug administration and incidence of venous thromboembolism (VTE) were assessed. Of 33 enrolled patients, laboratory and treatment data were available for 32 patients. Of these, 23 received pulsed dexamethasone (40 mg/day on days 1–4, 9–12 and 17–21 of each 28-day cycle) and 9 received weekly dexamethasone (40 mg/day on days 1, 8, 15 and 21 of each cycle). The overall incidence of VTE was 9%. A decreasing trend in markers values was observed with intercellular adhesion molecule (P = 0·05), fibrinogen (= 0·008), plasminogen activator inhibitor-1 (< 0·001), homocysteine (P = 0·002) and P–selectin (< 0·001) during therapy. Compared with weekly dexamethasone, pulsed dexamethasone was associated with significantly greater variation in mean adjusted relative values of fibrinogen, P-selectin and vascular endothelial growth factor (< 0·001 for all comparisons), although there was no apparent association with VTE incidence. Lenalidomide plus dexamethasone affects endothelial stress marker levels in patients with advanced MM. The higher variation seen with pulsed dexamethasone suggests greater endothelial stress with this approach.

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