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Update on the Diagnosis and Treatment of POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes) SyndromeA Review

Educational Objective
To learn the diagnosis and treatment strategies for POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome.
1 Credit CME
Abstract

Importance  POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare plasma cell disorder characterized by demyelinating peripheral neuropathy and clonal plasma cell proliferation. Clinical manifestations are believed to be associated with a surge of inflammatory and angiogenic mediators, including interleukins and vascular endothelial growth factor (VEGF), elicited by clonal and polyclonal plasma cells. The clinical manifestations of POEMS syndrome can be debilitating; therefore, early diagnosis is essential. This review discusses several aspects of POEMS syndrome and includes the most recently published findings, with a special emphasis on diagnosis and treatment strategies.

Observations  POEMS syndrome may be underdiagnosed because of its rarity, and it can be mistaken for chronic inflammatory demyelinating polyneuropathy; this misdiagnosis may lead to delayed therapy and progressive worsening of symptoms, especially neuropathy. Therefore, in addition to measurement of the VEGF level, patients with a monoclonal protein detected in blood and/or urine and neuropathy should be evaluated for POEMS syndrome with use of imaging to assess whether sclerotic bone lesions, effusions, and organomegaly are present. Clinical trials are scant, and treatment is largely based on small case series in which plasma cell–directed therapies, borrowed from the myeloma armamentarium, were used. High-dose melphalan and autologous hematopoietic cell transplantation may be offered to eligible patients. Lenalidomide and dexamethasone can be prescribed for patients who are ineligible for transplants. The main goals of therapy are to attain complete hematologic and VEGF responses and to reduce symptoms, although it may take up to 3 years for neurologic deficits to be ameliorated.

Conclusions and Relevance  POEMS syndrome should be considered in the differential diagnosis for patients who have peripheral neuropathy and paraproteinemia among other multisystem manifestations. The syndrome can be debilitating if not recognized early in its course; thus, appropriate diagnosis and treatment are important for optimal clinical outcomes.

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Article Information

Accepted for Publication: February 12, 2021.

Published Online: June 3, 2021. doi:10.1001/jamaoncol.2021.0586

Corresponding Author: Jack Khouri, MD, Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Floor CA6, 10201 Carnegie Ave, Cleveland, OH 44195 (khourij@ccf.org).

Author Contributions: Dr Khouri had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Khouri, Wong.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Khouri.

Critical revision of the manuscript for important intellectual content: All authors.

Administrative, technical, or material support: Nakashima.

Supervision: Khouri, Wong.

Conflict of Interest Disclosures: Dr Khouri reported receiving honoraria from Sanofi Genzyme and OncLive. Dr Nakashima reported receiving an honorarium from QualWorld and research funding from CellaVision. Dr Wong reported receiving consulting fees from Amgen, honoraria from Sanofi Genzyme, and research funding from Genentech, Bristol Myers Squibb, Fortis, Janssen, and GlaxoSmithKline.

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