Abstract Number: PB1957
Meeting: ISTH 2020 Congress
Background: The induction treatment for multiple myeloma (MM) patients has changed drastically in the last few years, including proteasome inhibitors (PI) and immunomodulatory agents. In parallel with these changes, the incidence of engraftment syndrome (ES), where endothelial damage implication cannot be disregarded, has increased.
Aims: Investigate whether the induction strategies (PI, such as bortezomib, together with immunomodulatory drugs, such as thalidomide, and dexamethasone) damage the endothelium, and explore the role of defibrotide (DF) as an endothelial protective agent.
Methods: Human microvascular endothelial cells (EC) in culture were exposed to the compounds (bortezomib -Velcade-, V; thalidomide, T; and dexamethasone, D) separately, or in combination without (VTD) and with DF (VTD+DF). Differences with control (no drug) were measured in markers of: i) inflammation (expression of ICAM-1 and adhesion of leukocytes under flow conditions, at the cell surface, ii) production of VWF, iii) cell permeability (VE-cadherin expression and cell monolayer integrity), and iv) oxidative stress (ROS production and eNOS expression).
Results: The expression of ICAM-1 and VWF were significantly higher in VTD but similar to control in VTD+DF. Separately, bortezomib demonstrated to be the main deleterious agent whereas dexamethasone showed no harmful effect. Leukocyte adhesion showed similar trends. VE-cadherin expression was significantly lower in VTD and slightly normalized in VTD+DF. EC permeability increased only with bortezomib. No significant changes were observed in ROS production and eNOS expression.
Conclusions: Our results demonstrate that bortezomib exerts the most damaging action on the endothelium in our in vitro approach, leading to a proinflammatory profile, increased expression of VWF, potentially modifying the prothrombotic behavior of the extracellular matrix, and compromised vascular integrity. Defibrotide prevents these damaging effects. A better knowledge of the mechanisms of the induction drugs will allow the design of effective protective measures to prevent the engraftment syndrome.
To cite this abstract in AMA style:
Martinez-Sanchez J, Palomo M, Torramade-Moix S, Moreno-Castaño AB, Rovira M, Gutiérrez-García G, Fernandez-Aviles F, Escolar G, Penack O, Rosiñol L, Carreras E, Diaz-Ricart M. The Induction Strategies Administered in the Treatment of Multiple Myeloma Exhibit a Deleterious Effect on the Endothelium [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-induction-strategies-administered-in-the-treatment-of-multiple-myeloma-exhibit-a-deleterious-effect-on-the-endothelium/. Accessed March 22, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-induction-strategies-administered-in-the-treatment-of-multiple-myeloma-exhibit-a-deleterious-effect-on-the-endothelium/