Incidence of Venous Thromboembolism in Multiple Myeloma Patients across Different Regimens: Role of Procoagulant Microparticles and Cytokine Release

Abstract

Introduction: Multiple myeloma (MM) is characterized by a high prevalence of thrombotic complications. Microvesicles (MVs) are small membrane vesicles released from activated cells, and they may potentially contribute to thrombosis. Methods: We have evaluated the plasma levels of MVs and cytokines (IL-10, IL-17, and TGF-β in MM and Watch and Wait Smoldering MM (WWSMM) from patients and related them to thrombotic complications. The secondary aim was to assess the impact of ongoing therapy on MV and on cytokine levels. Result: 92 MM and 31 WWSMM were enrolled, and 14 (12%) experienced a thrombotic episode. Using univariate analysis, TGF-β and MV were significantly higher in patients with thrombotic events (p = 0.012; p = 0.008, respectively). Utilizing a Cox proportional hazard model, we confirmed this difference (TGF-β p = 0.003; Odds ratio 0.001, 95% CI 0–0.003 and MV p = 0.001; Odds ratio 0.003, 95% CI 0.001–0.005). Active treatment management displayed higher levels of MV (p < 0.001) and lower levels of glomerular filtration-rate (p < 0.001), IL-17 (p < 0.001) as compared to the WWSMM group. The TGF-β values of immunomodulatory derivatives patients were lower in the WWSMM (p < 0.001) and Dexamethasone/Bortezomib subgroup (p < 0.001). Conclusion: The increased levels of MVs in active regimens add insight into the mechanisms of hypercoagulation in MM. In addition, a role for cytokine-related thrombosis is also suggested.