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

Abstract

ObjectivePOEMS (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.MethodThis 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.ResultsSerum 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.ConclusionsSerum 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.

POEMS syndrome: diagnostic delay and successful treatment with lenalidomide, cyclophosphamide and prednisone followed by autologous peripheral stem cell transplantation

“…Papilloedema decreased DLCO and depressed cardiac ejection fraction as seen in this patient are associated with poor outcomes 12. Serum VEGF levels, often used to monitor disease activity, may be a predictive biomarker for disease activity and prognosis 13. Treatment of POEMS syndrome requires both supportive care and specific treatments targeting underlying pathological plasma cells.…”

Increased IP-10 production by blood–nerve barrier in multifocal acquired demyelinating sensory and motor neuropathy and multifocal motor neuropathy

“…The serum VEGF concentration is clinically useful for monitoring disease activity in POEMS syndrome38; however, the role of serum VEGF in other immune-mediated neuropathies is still unclear. VEGF is a key regulator of barrier permeability in the blood-brain barrier (BBB) and BNB.…”

Proposal of new clinical diagnostic criteria for POEMS syndrome

“…Assessments of each manifestation was performed as follows: (1) polyneuropathy: distal-dominant sensory and motor symptoms, hyporeflexia or areflexia and evidence of demyelination confirmed by systematic nerve conduction studies; (2) monoclonal plasma cell proliferative disorder: M-protein detected by serum immunofixation or monoclonal plasma cell proliferation revealed by bone mallow aspiration/biopsy. Identification of plasma cell clonality was assessed by immunohistostaining, in situ hybridisation and/or flow cytometry ; (3) serum VEGF elevation: >1000 pg/mL measured by ELISA (Special Reference Laboratory, Tokyo, Japan)14; (4) extravascular volume overload: oedema or effusion detected by chest and abdominal CT scan; (5) skin changes: evident hyperpigmentation, hypertrichosis, glomeruloid haemangiomata, white nails or cyanosis; (6) organomegaly: hepatosplenomegaly or lymphadenopathy demonstrated by CT scan or ultrasonography; (7) sclerotic bone lesions: bone sclerosis detected by X-ray or CT, bone or positron emission tomography scans; (8) endocrinopathy: consistent clinical features and each hormonal abnormality; (9) papilloedema: evaluation by an ophthalmologists or neurologists; (10) thrombocytosis: blood platelet count >350×10 9 /L and (11) Castleman disease: characteristic clinical and laboratory features and lymph node biopsy findings.…”