POEMS syndrome: Update on diagnosis, risk-stratification, and management
Dispenzieri A · Am J Hematol · 2023
- ●Most comprehensive and current review of POEMS syndrome
- ●Updated treatment algorithms including daratumumab combinations
Sources & References
33 published sources for POEMS Syndrome, each with evidence grades and key findings.
33 total sourcesGrade A: 4Grade B: 26Grade C: 3reviews (6)genetics (5)treatment (9)epidemiology (3)clinical (3)diagnostics (5)pathophysiology (2)
reviews
6 sources
POEMS syndrome: 2021 Update on diagnosis, risk-stratification, and management
Dispenzieri A · Am J Hematol · 2021
- ●Updated treatment landscape including bortezomib-based regimens
- ●Risk stratification: albumin, age, pleural effusion, pulmonary hypertension, eGFR
POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management
Dispenzieri A · Am J Hematol · 2019
- ●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
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
POEMS syndrome
Dispenzieri A · Blood Rev · 2007
- ●Comprehensive review of diagnosis and management
- ●VEGF as confirmatory biomarker
- ●Treatment algorithm based on disease extent
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
genetics
5 sources
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
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
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
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
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
treatment
9 sources
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
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
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
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%)
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%
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
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
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%)
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
epidemiology
3 sources
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%
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%
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
clinical
3 sources
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
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
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
diagnostics
5 sources
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
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
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
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
Patterns of nerve conduction abnormalities in POEMS syndrome
Sung JY, Kuwabara S, Ogawara K, Kanai K, Hattori T · Muscle Nerve · 2002
- ●Slowing more predominant in intermediate than distal nerve segments
- ●Rare conduction block (6% of tested nerves)
- ●More severe CMAP attenuation in lower than upper limbs
pathophysiology
2 sources
Markedly upregulated serum interleukin-12 as a novel biomarker in POEMS syndrome
Kanai K, Kuwabara S, Misawa S, Hattori T · Neurology · 2012
- ●IL-12 and VEGF markedly elevated in all POEMS patients
- ●IL-12 and VEGF decrease with treatment, correlating with clinical improvement
- ●IL-12 proposed as novel biomarker of disease activity
Overproduction of proinflammatory cytokines imbalanced by their antagonists in POEMS syndrome
Gherardi RK, Belec L, Soubrier M, et al. · Blood · 1996
- ●IL-1beta, TNF-alpha, IL-6 elevated in POEMS vs myeloma
- ●TGF-beta1 decreased — weak antagonistic reaction
- ●Proinflammatory cytokine network drives disease manifestations