●Updated Dispenzieri diagnostic criteria with mandatory, major, and minor criteria
●VEGF elevated as major criterion alongside sclerotic bone lesions and Castleman disease
●10-year OS approaching 80% in modern era

Details DOI ↗

Grade Bnarrative review

POEMS syndrome

Keddie S, Lunn MP · Curr Opin Neurol · 2018

●VEGF is a useful and accurate biomarker for diagnosis and disease monitoring
●Overview of prognostic factors and treatment outcomes

Details PubMed ↗

Grade Bnarrative review

POEMS syndrome

Dispenzieri A · Blood Rev · 2007

●Comprehensive review of diagnosis and management
●VEGF as confirmatory biomarker
●Treatment algorithm based on disease extent

Details DOI ↗

Grade Bcase series

Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes: the POEMS syndrome

Bardwick PA, Zvaifler NJ, Gill GN, Newman D, Greenway GD, Resnick DL · Medicine (Baltimore) · 1980

●Coined the POEMS acronym
●Defined the five cardinal features of the syndrome

Details PubMed ↗

genetics

5 sources

Grade Bcohort

Unraveling unique features of plasma cell clones in POEMS syndrome with single-cell analysis

Isshiki T, Yaguchi T, Okuyama Y, et al. · JCI Insight · 2022

●POEMS clones identified via single-cell RNA-Seq with IGLV1-36, -40, -44, -47 sequences
●POEMS clones are CD19+, CD138+, MHC class II-low
●VEGF mRNA not upregulated in POEMS clones — VEGF not produced by clonal plasma cells
●IL-6 expression increased in POEMS clones, a known inducer of VEGF

Details DOI ↗

Grade Bcohortn=42

A highly heterogeneous mutational pattern in POEMS syndrome

Chen J, Gao XM, Zhao H, et al. · Leukemia · 2021

●170 somatic mutations in exonic regions from 10 patients via WES
●Significantly mutated genes: LILRB1 (10%), HEATR9 (20%), FMNL2 (10%)
●Driver genes including MYD88, NFKB2, STAT3, CUX1 identified
●Heterogeneous genomic profiles distinct from multiple myeloma

Details DOI ↗

Grade Bcohort

Immunoglobulin variable domain high-throughput sequencing reveals specific novel mutational patterns in POEMS syndrome

Abe D, Sakaue T, Kamata T, et al. · Blood · 2020

●Stereotypic amino acid changes in CDR1 and FR2 regions of IGLV1-40 and IGLV1-44
●Specific mutational patterns unique to POEMS syndrome
●Supports pathogenic role of restricted light chain gene usage

Details DOI ↗

Grade Bcohortn=20

Genetic and transcriptional landscape of plasma cells in POEMS syndrome

Nagao Y, Mimura N, Takeda J, et al. · Leukemia · 2019

●308 somatic mutations in 285 genes via WES in 11 patients
●Recurrently mutated genes: KLHL6, LTB, EHD1, EML4, HEPHL1, HIPK1, PCDH10
●No myeloma driver genes (NRAS, KRAS, BRAF, TP53) detected
●Transcription profile specific to POEMS vs MGUS and myeloma

Details DOI ↗

Grade Bcase seriesn=11

Restrictive usage of monoclonal immunoglobulin lambda light chain germline in POEMS syndrome

Abe D, Nakaseko C, Takeuchi M, et al. · Blood · 2008

●IGL V-region restricted to Vlambda1 subfamily in all 11 patients
●IGLV1-44*01 (9/11) and IGLV1-40*01 (2/10) germlines identified
●IGLJ3*02 gene used in all 11 rearrangements

Details DOI ↗

treatment

9 sources

Grade Bcohortn=69

Bortezomib plus dexamethasone as first-line therapy for patients with POEMS syndrome

He H, Zhao D, Jiang H, et al. · Ann Hematol · 2021

●Best neurologic response 88.1%
●Hematologic CR 46.4%, VEGF response 71.2%
●Only 2 patients with grade 1 bortezomib-induced neuropathy (reversible)
●No treatment-related deaths

Details DOI ↗

Grade Bcohortn=347

What is the best first-line treatment for POEMS syndrome: autologous transplantation, melphalan and dexamethasone, or lenalidomide and dexamethasone?

Zhao H, Cai H, Wang C, et al. · Am J Hematol · 2019

●Compared ASCT (n=165), MDex (n=79), LDex (n=103) as first-line therapy
●ASCT achieved highest hematologic CR (49.7%)
●Neurological remission similar across groups (~93%)
●3-year PFS 80.5%, 3-year OS 90.8% overall

Details DOI ↗

Grade Bcohortn=41

A prospective phase II study of low dose lenalidomide plus dexamethasone in patients with newly diagnosed POEMS syndrome

He H, Zhao D, Jiang H, et al. · Am J Hematol · 2018

●Complete hematologic response 46%, neurologic response 95%
●VEGF response 83%, median time to response 2 months
●3-year OS 90%, 3-year PFS 75%
●No treatment-related deaths or grade 3+ lenalidomide adverse events

Details DOI ↗

Grade ARCT

Safety and efficacy of thalidomide in patients with POEMS syndrome: a multicentre, randomised, double-blind, placebo-controlled trial

Misawa S, Sato Y, Katayama K, et al. · Lancet Neurol · 2016

●Only RCT in POEMS syndrome (J-POST trial)
●VEGF reduction rate 0.39 with thalidomide vs -0.02 with placebo (p=0.04)
●Sinus bradycardia more frequent with thalidomide (54% vs 0%)

Details DOI ↗

Grade Ccohortn=12

Efficacy and safety of low-dose lenalidomide plus dexamethasone in patients with relapsed or refractory POEMS syndrome

Li J, Zhang W, Jiao L, et al. · Eur J Haematol · 2015

●Overall hematologic response 77%, complete response 44%
●Neurological response 67%
●VEGF response 91%

Details DOI ↗

Grade Bcohortn=38

Outcomes of patients with POEMS syndrome treated initially with radiation

Humeniuk MS, Gertz MA, Lacy MQ, et al. · Blood · 2013

●Radiation as initial therapy for patients with 1-3 bone lesions
●4-year OS 97%, 4-year event-free survival 52%
●Median radiation dose 45 Gy
●Potentially curative for isolated plasmacytoma

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Grade Ccase seriesn=6

Ambiguous effects of anti-VEGF monoclonal antibody (bevacizumab) for POEMS syndrome

Kanai K, Kuwabara S, Misawa S, Hattori T · J Neurol · 2013

●VEGF levels decreased after bevacizumab in all patients
●4 of 6 patients had no clinical response, 2 died
●Inhibiting VEGF alone may be insufficient — multiple cytokines upregulated

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Grade Bcohortn=59

Long-term outcomes after autologous stem cell transplantation for patients with POEMS syndrome (osteosclerotic myeloma): a single-center experience

D'Souza A, Lacy M, Gertz M, et al. · Blood · 2012

●PFS 98% at 1 year, 75% at 5 years after ASCT
●Clinical improvement nearly universal
●VEGF response before ASCT predicted better 5-year PFS (90.9% vs 47.4%)

Details DOI ↗

Grade Bcohortn=31

Combination of melphalan and dexamethasone for patients with newly diagnosed POEMS syndrome

Li J, Zhou DB, Huang Z, et al. · Blood · 2011

●Hematologic response 80.6% (CR 38.7%, PR 41.9%)
●Neurologic response 100%
●Pulmonary hypertension resolved in 93.3%
●Low toxicity profile

Details DOI ↗

epidemiology

3 sources

Grade Bcohortn=392

Prevalence, clinical profiles, and prognosis of POEMS syndrome in Japanese nationwide survey

Suichi T, Misawa S, Sato Y, et al. · Neurology · 2019

●Estimated prevalence 0.3 per 100,000 in Japan
●Median age at onset 54 years
●Male:female ratio 1.5:1
●10-year overall survival 93%

Details DOI ↗

Grade Bcohortn=262

Risk factors for and outcomes of patients with POEMS syndrome who experience progression after first-line treatment

Kourelis TV, Buadi FK, Kumar SK, et al. · Am J Hematol · 2016

●5-year PFS 58%, 5-year OS 78%
●30% experienced relapse/progression
●Median time to relapse/progression 42 months
●Complete hematologic response associated with PFS of 88%

Details DOI ↗

Grade Bcohortn=99

POEMS syndrome: definitions and long-term outcome

Dispenzieri A, Kyle RA, Lacy MQ, et al. · Blood · 2003

●Proposed formal diagnostic criteria for POEMS syndrome
●Median overall survival of 13.8 years
●Identified pulmonary hypertension, renal failure, thrombosis as complications

Details DOI ↗

clinical

3 sources

Grade Bcohortn=54

Prevalence and Course of Endocrinopathy in POEMS Syndrome

Caimari F, Keddie S, Lunn MP, et al. · J Clin Endocrinol Metab · 2019

●63% presented with endocrinopathy at diagnosis, 92% developed one during follow-up
●Hypogonadism most common, followed by hyperprolactinemia (56%), hypothyroidism
●Baseline hypothyroidism associated with inferior PFS and OS

Details DOI ↗

Grade Bcohortn=107

Cutaneous manifestations in patients with POEMS syndrome

Shi X, Luo Y, Zhang L, et al. · Am J Med · 2013

●90% of patients had cutaneous manifestations
●Hyperpigmentation and hemangioma most common (47%)
●Hypertrichosis 38%, acrocyanosis 34%, sclerodermoid changes 26%
●Glomeruloid hemangioma in ~3%, highly specific for POEMS

Details PubMed ↗

Grade Bcohortn=64

Endocrinopathy in POEMS syndrome: the Mayo Clinic experience

Gandhi GY, Basu R, Dispenzieri A, Basu A, Montori VM, Brennan MD · Mayo Clin Proc · 2007

●84% had recognized endocrinopathy
●Hypogonadism most common (79% of men)
●Hypothyroidism, glucose intolerance, adrenal insufficiency also prevalent

Details DOI ↗

diagnostics

5 sources

Grade Bcohort

Raised VEGF: High sensitivity and specificity in the diagnosis of POEMS syndrome

Pihan M, Keddie S, D'Sa S, et al. · Neurol Neuroimmunol Neuroinflamm · 2018

●Serum VEGF >1000 pg/mL with demyelinating neuropathy and lambda monoclonal protein: 100% sensitivity, 93% specificity
●Elevated sVEGF sensitivity 100%, specificity 91% for POEMS in neuropathy patients

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Grade Bcohort

Uniform demyelination and more severe axonal loss distinguish POEMS syndrome from CIDP

Mauermann ML, Sorenson EJ, Dispenzieri A, et al. · J Neurol Neurosurg Psychiatry · 2012

●POEMS shows uniform demyelination (intermediate segments) vs multifocal in CIDP
●Greater axonal loss in POEMS than CIDP
●Less temporal dispersion and conduction block in POEMS
●Terminal latency index may distinguish the two disorders

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Grade Bcohort

Different neurological and physiological profiles in POEMS syndrome and chronic inflammatory demyelinating polyneuropathy

Nasu S, Misawa S, Sekiguchi Y, et al. · J Neurol Sci · 2012

●POEMS patients have less prolonged distal motor latency than CIDP
●Higher terminal latency index in POEMS vs CIDP
●Demyelination predominant in nerve trunk rather than distal terminals

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Grade Bcohortn=29

The utility of plasma vascular endothelial growth factor levels in the diagnosis and follow-up of patients with POEMS syndrome

D'Souza A, Hayman SR, Buadi F, et al. · Blood · 2011

●Plasma VEGF differentiates POEMS from other plasma cell dyscrasias and neuropathies
●Plasma VEGF avoids platelet-derived VEGF confounding (serum)
●Plasma VEGF useful for monitoring treatment response

Details DOI ↗

Grade Ccohortn=8