A new study suggests higher levels of microvesicles (MVs) are present in the plasma of patients with multiple myeloma (MM), with possible implications suggested for levels of inflammatory cytokines and for thrombosis risk. The study investigators reported their findings in the Journal of Clinical Medicine.
Patients with MM have an elevated risk of venous thromboembolism (VTE), the study investigators explained in their report. Additionally, VTE incidence differs with varied treatment regimens. The investigators also indicated that research has suggested MVs may play a role in mediating the conditions for thrombosis.
From the plasma of actively treated patients with MM and patients with Watch-and-Wait Smoldering MM (WWSMM), the researchers assessed levels of MVs and cytokines, including interleukin (IL)-10, IL-17, and transforming growth factor (TGF)-beta. A primary goal was to examine relationships between these factors and thrombotic complications, with a secondary goal of evaluating effects of continued treatment on levels of MVs and cytokines. Treated patients were receiving either dexamethasone plus bortezomib or treatment based on immunotherapy derivatives (IMiDS).
A total of 92 actively treated patients with MM, and 31 patients with WWSMM, were evaluated. Among treated patients, 29 were receiving dexamethasone and bortezomib, and 63 were receiving IMiDS. Thrombotic episodes occurred in 14 patients (12%) overall. A univariate analysis suggested there were higher levels of MVs (P =.008) and TGF-beta (P =.012) in patients experiencing thrombosis, compared with those without thrombosis.
The concentration of MVs in the plasma of patients with thrombosis was 1100 N/mL (interquartile range [IQR], 1087-1200), and it was 1100 N/mL (IQR, 200-1200) in patients without thrombosis. Concentrations of TGF-beta were 1470 ng/mL (IQR, 1180-3145) in patients with thrombosis, compared with 700 (IQR, 300-2360) in patients without thrombosis. Multivariate analysis suggested these levels were significantly different with and without thrombosis for both MVs (P =.001) and TGF-beta (P =.003).
Thrombotic events also appeared to be associated with active treatment (P =.02), with all thrombotic events in this study occurring in patients receiving active treatment. This included 10 patients receiving dexamethasone plus bortezomib and 4 receiving IMiDS.
Compared with patients in the WWSMM group, patients who were receiving active therapy had significantly higher concentrations of MVs (P <.001), but lower concentrations of IL-17 (P <.001). The researchers suggested lower IL-17 levels could reflect response in treated patients.
TGF-beta levels were significantly higher in patients with WWSMM than in patients receiving IMiDS (P <.001). Patients receiving dexamethasone and bortezomib had a TGF-beta levels that were not significantly different from those with WWSMM (P =.11) but were significantly higher than in patients receiving IMiDS (P <.001). The researchers suggested these findings could potentially relate to a capacity for IMiDS to modulate cytokine levels.
“To conclude, this is the first prospective study correlating MVs levels with different inflammatory cytokines in MM,” the investigators wrote in their report. “Overall, we found that MVs increase in treated MM patients across different regimens,” they continued. They also suggested a role for cytokine-mediated thrombosis should be further explored.
Gidaro A, Manetti R, Palmerio Delitala A, et al. Incidence of venous thromboembolism in multiple myeloma patients across different regimens: role of procoagulant microparticles and cytokine release. J Clin Med. 2022;11(10):2720. doi:10.3390/jcm11102720