Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response: retrospective cohort study

Abstract

Objective: POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare multisystem disease characterised by plasma cell dyscrasia and overproduction of vascular endothelial growth factor (VEGF). VEGF is assumed to be useful in monitoring disease activity, because VEGF levels usually decrease after treatment. However, there is no study to investigate whether the extent of decrease in VEGF correlates with clinical outcome. We tested the predictive efficacy of serum VEGF levels in POEMS syndrome.

Method: This was an institutional review board approved retrospective observational cohort study of 20 patients with POEMS monitored regularly for more than 12 months (median follow-up, 87 months) after treatment onset using our prospectively accumulated database of POEMS from 1999 to 2015. Patients were treated by autologous peripheral blood stem cell transplantation or thalidomide administration. Serum VEGF was measured by ELISA. Outcome measures included clinical and laboratory findings and relapse-free survival.

Results: Serum VEGF levels decreased rapidly after treatment, and stabilised by 6 months post treatment. Patients with normalised serum VEGF levels (<1040 pg/mL) at 6 months showed prolonged relapse-free survival (HR=12.81, 95% CI 2.691 to 90.96; p=0.0001) and greater later clinical improvement. The rate of serum VEGF reduction over the first 6 months post treatment correlated with increased grip strength, serum albumin levels, and compound muscle action potential amplitudes at 12 months.

Conclusions: Serum VEGF level at 6 months post treatment is a predicative biomarker for disease activity and prognosis in POEMS syndrome. Serum VEGF could be used as a surrogate endpoint for relapse-free survival or clinical or laboratory improvement of POEMS syndrome for clinical trials.

Figure 1

Changes in serum vascular endothelial growth factor (VEGF) after treatment. (A) Autologus peripheral blood stem cell transplantation with high-dose chemotherapy (n=12). (B) Thalidomide–dexamethasone therapy (n=8).

Figure 2

Kaplan–Meier plot for relapse-free survival. Patients with vascular endothelial growth factor (VEGF) <1040 pg/mL at 6 months after treatment showed significant longer relapse-free survival than patients with VEGF≥1040 pg/mL (HR=12.81, 95% CI 2.691 to 90.96; p=0.0001).

Figure 3

Changes in clinical or laboratory measures at 12 months post treatment. (A) Grip strength. (B) Serum albumin. (C) Compound muscle action potential (CMAP) amplitude of the median nerve. Patients with serum vascular endothelial growth factor (VEGF) <1040 pg/mL at 6 months after treatment showed significant improvements in all parameters compared with patients with VEGF ≥1040 pg/mL.

Figure 4

Correlation between reduction rate of vascular endothelial growth factor (VEGF) at 6 months after treatment and changes in grip strength (A), serum albumin (B), and CMAP amplitude of the median nerve (C) at 12 months after treatment. The grater the rate of VEGF decline at 6 months of treatment, the better the clinical and laboratory findings at 12 months.