Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response

Retrospective cohort study

S. Misawa, Yasunori Sato, K. Katayama, H. Hanaoka, S. Sawai, M. Beppu, F. Nomura, K. Shibuya, Y. Sekiguchi, Y. Iwai, K. Watanabe, H. Amino, C. Ohwada, M. Takeuchi, E. Sakaida, C. Nakaseko, S. Kuwabara

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 relapsefree 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 relapsefree 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.

Original languageEnglish
Article numbere009157
JournalBMJ open
Volume5
Issue number11
DOIs
Publication statusPublished - 2015 Jan 1
Externally publishedYes

Fingerprint

POEMS Syndrome
Vascular Endothelial Growth Factor A
Cohort Studies
Retrospective Studies
Serum
Therapeutics
Survival
Biomarkers
Peripheral Blood Stem Cell Transplantation
Skin
Paraproteinemias
Thalidomide
Research Ethics Committees
Hand Strength
Rare Diseases
Serum Albumin
Action Potentials
Observational Studies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Misawa, S., Sato, Y., Katayama, K., Hanaoka, H., Sawai, S., Beppu, M., ... Kuwabara, S. (2015). Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response: Retrospective cohort study. BMJ open, 5(11), [e009157]. https://doi.org/10.1136/bmjopen-2015-009157

Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response : Retrospective cohort study. / Misawa, S.; Sato, Yasunori; Katayama, K.; Hanaoka, H.; Sawai, S.; Beppu, M.; Nomura, F.; Shibuya, K.; Sekiguchi, Y.; Iwai, Y.; Watanabe, K.; Amino, H.; Ohwada, C.; Takeuchi, M.; Sakaida, E.; Nakaseko, C.; Kuwabara, S.

In: BMJ open, Vol. 5, No. 11, e009157, 01.01.2015.

Research output: Contribution to journalArticle

Misawa, S, Sato, Y, Katayama, K, Hanaoka, H, Sawai, S, Beppu, M, Nomura, F, Shibuya, K, Sekiguchi, Y, Iwai, Y, Watanabe, K, Amino, H, Ohwada, C, Takeuchi, M, Sakaida, E, Nakaseko, C & Kuwabara, S 2015, 'Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response: Retrospective cohort study', BMJ open, vol. 5, no. 11, e009157. https://doi.org/10.1136/bmjopen-2015-009157
Misawa, S. ; Sato, Yasunori ; Katayama, K. ; Hanaoka, H. ; Sawai, S. ; Beppu, M. ; Nomura, F. ; Shibuya, K. ; Sekiguchi, Y. ; Iwai, Y. ; Watanabe, K. ; Amino, H. ; Ohwada, C. ; Takeuchi, M. ; Sakaida, E. ; Nakaseko, C. ; Kuwabara, S. / Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response : Retrospective cohort study. In: BMJ open. 2015 ; Vol. 5, No. 11.
@article{2c303ef84492432297ad977c93cc9511,
title = "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 relapsefree 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 relapsefree 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.",
author = "S. Misawa and Yasunori Sato and K. Katayama and H. Hanaoka and S. Sawai and M. Beppu and F. Nomura and K. Shibuya and Y. Sekiguchi and Y. Iwai and K. Watanabe and H. Amino and C. Ohwada and M. Takeuchi and E. Sakaida and C. Nakaseko and S. Kuwabara",
year = "2015",
month = "1",
day = "1",
doi = "10.1136/bmjopen-2015-009157",
language = "English",
volume = "5",
journal = "BMJ Open",
issn = "2044-6055",
publisher = "BMJ Publishing Group",
number = "11",

}

TY - JOUR

T1 - Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response

T2 - Retrospective cohort study

AU - Misawa, S.

AU - Sato, Yasunori

AU - Katayama, K.

AU - Hanaoka, H.

AU - Sawai, S.

AU - Beppu, M.

AU - Nomura, F.

AU - Shibuya, K.

AU - Sekiguchi, Y.

AU - Iwai, Y.

AU - Watanabe, K.

AU - Amino, H.

AU - Ohwada, C.

AU - Takeuchi, M.

AU - Sakaida, E.

AU - Nakaseko, C.

AU - Kuwabara, S.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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 relapsefree 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 relapsefree 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.

AB - 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 relapsefree 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 relapsefree 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.

UR - http://www.scopus.com/inward/record.url?scp=84947262749&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947262749&partnerID=8YFLogxK

U2 - 10.1136/bmjopen-2015-009157

DO - 10.1136/bmjopen-2015-009157

M3 - Article

VL - 5

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 11

M1 - e009157

ER -