Regular assessment of serum vascular endothelial growth factor levels to monitor POEMS syndrome

Abstract

Background: To investigate the utility of regular serum VEGF (sVEGF) levels assessment in the monitoring of POEMS syndrome.

Methods: We retrospectively reviewed data of 30 patients with POEMS syndrome whose sVEGF was tested regularly every 6 months. sVEGF levels after treatment were measured and correlated with disability (Overall Neuropathy Limitations Scale, ONLS), clinical impairment (measured with the modified Clinical Response Evaluation Scale, mCRES), and relapse-free survival. The ability of sVEGF to predict disease flares during remission and refractory disease was also analysed.

Results: Patients with normalised serum VEGF levels (< 1000 pg/ml) at 6 months showed prolonged relapse-free survival (at 3-year 94% for complete VEGF response, 57% partial, 0% none, p < 0.001) and greater later clinical improvement (median ΔmCRES complete VEGF response -5 vs partial -4, p = 0.019, and vs no VEGF response -2, p = 0.006). After remission, the sensitivity of 6-month sVEGF monitoring in predicting clinical relapse was 58% with a specificity of 100%. In patients refractory to treatment, the sensitivity in predicting further clinical worsening was 15%. In addition, in 25% of the patients in remission and 16% of those refractory to therapy, sVEGF levels only increased at the time of relapse.

Conclusions: Regular sVEGF assessment is a valid biomarker in the prediction of disease reactivation in POEMS syndrome and was particularly useful during the phase of remission.

Keywords: Biomarker; Monitoring; Neuropathy; POEMS syndrome; Relapse; VEGF.

Fig. 1

Examples of sVEGF changes (red) in relation to clinical (green) and neurological (blue) scores during follow-up. A sVEGF rise anticipating clinical worsening. B Pathologic sVEGF rise occurring only at time of clinical relapse. C A case developing disease worsening in the absence of significant sVEGF rise. D Criteria for sVEGF progression were met in a patient with negative follow-up while on treatment with lenalidomide

Fig. 2

Kaplan–Meier survival curves of patients with POEMS syndrome treated at study entry divided according to sVEGF response after 6 months (A) and after 12 months (B) after therapy. A complete sVEGF response after 6 months was significantly associated with better relapse-free survival compared to no sVEGF response (CR_VEGF vs NR_VEGF, p = 0.015) but there was no difference with partial sVEGF response (CR_VEGF vs PR_VEGF, p = 0.61). Instead, a CR at 12 months showed a longer relapse-free survival compared to both no or partial sVEGF (CR_VEGF vs NR_VEGF, p = 0.001; CR_VEGF vs PR_VEGF, p = 0.005)