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VE-CADHERIN IN MULTIPLE MYELOMA: AN INDEPENDENT PROGNOSTIC FACTOR FOR PROGRESSION-FREE SURVIVAL
Author(s):
Borys Samura
,
Borys Samura
Affiliations:
Department of Hematology,Zaporizhzhia Regional Clinical Hospital,Zaporizhzhia,Ukraine;Department of Internal diseases,Zaporizhzhia State Medical University,Zaporizhzhia,Ukraine
Yuriy Kolesnyk
,
Yuriy Kolesnyk
Affiliations:
Department of Pathophysiology,Zaporizhzhia State Medical University,Zaporizhzhia,Ukraine
Vitaliy Syvolap
,
Vitaliy Syvolap
Affiliations:
Department of Propedeutics of Internal Diseases,Zaporizhzhia State Medical University,Zaporizhzhia,Ukraine
Andriy Abramov
Andriy Abramov
Affiliations:
Scientific medical-laboratory center,Zaporizhzhia State Medical University,Zaporizhzhia,Ukraine
(Abstract release date: 05/18/17) EHA Library. Samura B. 05/18/17; 182716; PB2002
Boris Samura
Boris Samura
Contributions
PDF Abstract
Abstract

Abstract: PB2002

Type: Publication Only

Background

Endothelial damage and perivascular infiltrates are vital in the development of multiple myeloma. Recent studies have found that endothelial dysfunction might be result in multiple myeloma progression and adverse effects of drug implementation. On the other hand, there is a direct correlation between microvessel density in multiple myeloma and parameters of disease progression. Endothelial cells participate in inflammatory events leading to atherogenesis by regulating endothelial cell permeability via the expression vascular endothelial-cadherin (VE-Cadherin) on their surface. VE-cadherin is cell adhesion molecules localized at the endothelial junction, which plays critical roles in angiogenesis, neovascularization, neoplasm development, stem cells mobbing, and endothelial integrity. Indeed, VE-cadherin chiefly organizes the opening and closing of the endothelial barrier. It has found that VE-cadherin as a transmembrane protein probably modulates intensity of angiogenesis in multiple myeloma and may be useful in prognosis. However, the predictive role of VE-cadherin as a prognostic factor for survival of patients after treatment of multiple myeloma is not still clear.

Aims
We aimed to evaluate the prognostic value of circulating VE-catherin for progression-free survival in patients with multiple myeloma in complete or partial remission.

Methods
One hundred twelve out subjects with multiple myeloma were enrolled in the study. Diagnosis and staging of multiple myeloma were defined by current clinical practice guidelines. To be achieving remission chemotherapy with bortezomib, thalidomide, dexamethasone, cyclophosphamide, melphalan, anthracyclines was used accordingly contemporary clinical guidelines. All subjects were at complete or partial remission at baseline. Observation period was up to 12 months. ELISA method for measurements of circulating level of VE-catherin was used.

Results

Medians of circulating levels of VE-catherin in subjects without progression of multiple myeloma (n=89) and subjects with progression (n=23) during 12 months were 0.92 ng/ml (95% confidence interval [CI] = 0.66-1.19 ng/ml) and 1.77 ng/ml (95% CI = 1.47-2.07 ng/ml) (р=0.0002). The best VE-catherin cutoff value for predicting disease progression risk was 1.31 ng/mL with AUC value 0.839 (p=0.0001), the sensitivity and specificity were 77.8% and 61.5% respectively.
The presence of high levels of serum VE-cadherin was significantly correlated to a shorter progression-free survival (PFS). In a multivariate analysis along with clinical and biologic prognostic parameters, high serum VE-cadherin level (>1.31 ng/ml) was an independent adverse prognostic variable for PFS (median PFS 9.93 (IC = 8.16-11.71) months vs 7.35 (IC = 5.75-8.95) months (p=0.02).

Conclusion
The serum VE-cadherin level is a valuable biomarker for predicting treatment response and an independent prognostic factor for progression-free survival for patients with multiple myeloma.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Survival, Prognostic factor, Myeloma

Abstract: PB2002

Type: Publication Only

Background

Endothelial damage and perivascular infiltrates are vital in the development of multiple myeloma. Recent studies have found that endothelial dysfunction might be result in multiple myeloma progression and adverse effects of drug implementation. On the other hand, there is a direct correlation between microvessel density in multiple myeloma and parameters of disease progression. Endothelial cells participate in inflammatory events leading to atherogenesis by regulating endothelial cell permeability via the expression vascular endothelial-cadherin (VE-Cadherin) on their surface. VE-cadherin is cell adhesion molecules localized at the endothelial junction, which plays critical roles in angiogenesis, neovascularization, neoplasm development, stem cells mobbing, and endothelial integrity. Indeed, VE-cadherin chiefly organizes the opening and closing of the endothelial barrier. It has found that VE-cadherin as a transmembrane protein probably modulates intensity of angiogenesis in multiple myeloma and may be useful in prognosis. However, the predictive role of VE-cadherin as a prognostic factor for survival of patients after treatment of multiple myeloma is not still clear.

Aims
We aimed to evaluate the prognostic value of circulating VE-catherin for progression-free survival in patients with multiple myeloma in complete or partial remission.

Methods
One hundred twelve out subjects with multiple myeloma were enrolled in the study. Diagnosis and staging of multiple myeloma were defined by current clinical practice guidelines. To be achieving remission chemotherapy with bortezomib, thalidomide, dexamethasone, cyclophosphamide, melphalan, anthracyclines was used accordingly contemporary clinical guidelines. All subjects were at complete or partial remission at baseline. Observation period was up to 12 months. ELISA method for measurements of circulating level of VE-catherin was used.

Results

Medians of circulating levels of VE-catherin in subjects without progression of multiple myeloma (n=89) and subjects with progression (n=23) during 12 months were 0.92 ng/ml (95% confidence interval [CI] = 0.66-1.19 ng/ml) and 1.77 ng/ml (95% CI = 1.47-2.07 ng/ml) (р=0.0002). The best VE-catherin cutoff value for predicting disease progression risk was 1.31 ng/mL with AUC value 0.839 (p=0.0001), the sensitivity and specificity were 77.8% and 61.5% respectively.
The presence of high levels of serum VE-cadherin was significantly correlated to a shorter progression-free survival (PFS). In a multivariate analysis along with clinical and biologic prognostic parameters, high serum VE-cadherin level (>1.31 ng/ml) was an independent adverse prognostic variable for PFS (median PFS 9.93 (IC = 8.16-11.71) months vs 7.35 (IC = 5.75-8.95) months (p=0.02).

Conclusion
The serum VE-cadherin level is a valuable biomarker for predicting treatment response and an independent prognostic factor for progression-free survival for patients with multiple myeloma.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Survival, Prognostic factor, Myeloma

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