Recent Advances in the Treatment and Supportive Care of POEMS Syndrome

Abstract

POEMS is a rare clonal plasma cell disorder characterized by multi-systemic features that include demyelinating peripheral neuropathy, organomegaly, endocrinopathy, presence of monoclonal proteins (M-protein), and skin changes. Even though the pathophysiology is poorly understood, recent studies suggest that both clonal and polyclonal plasmacytosis leading to the production of pro-inflammatory cytokines and angiogenic mediators play the central role. These mediators including vascular endothelial growth factor (VEGF) are the driving forces of the syndrome. The diagnosis of POEMS is not always straight forward and often the diagnosis is delayed. It is based on fulfilling mandatory criteria of polyradiculoneuropathy and monoclonal protein and the presence of one major criterion (Castleman disease, sclerotic bone lesions, or elevated VEGF), and at least one minor criterion. Due to the presence of neuropathy, it can be confused with chronic inflammatory demyelinating polyradiculopathy (CIDP), and if thrombocytosis and splenomegaly are present, it can be confused with myeloproliferative neoplasms. Due to the rarity of the syndrome, clear guidelines for treatment are still lacking. Immediate treatment targeting the underlying plasma cell proliferation results in a dramatic response in most patients. The key is early diagnosis and immediate anti-plasma cell directed therapy for the best clinical outcomes. For patients with disseminated disease as defined by bone marrow involvement or more than three osteosclerotic bone lesions, high-dose chemotherapy with autologous hematopoietic stem cell transplant (ASCT) yields durable responses and is the preferred treatment in eligible patients. For patients with localized bony disease, radiotherapy has proven to be very effective. Lenalidomide and dexamethasone is a proven therapy in patients ineligible for ASCT. In this review article, we tackle the diagnostic approach and discuss the latest treatment modalities of this rare debilitating disease.

Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome with dilated cardiomyopathy: A case report

“…Recently, treatments that target the plasma cells that produce the M-protein have shown excellent clinical responses. This suggests that the M-protein might be one of the driving factors of the disease[ 11 ]. Additionally, patients with an M-protein restricted to clonal immunoglobulin λ light variable chain -1-40 experienced severe clinical symptoms[ 12 ].…”

Unraveling the Neurological Complexity of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Protein, and Skin Changes Syndrome: A Report of a Challenging Case of a Young Woman and Cutting-Edge Advancements in the Field

“…Before initiating therapy, it is of utmost importance to confirm whether the patient meets the criteria for plasma cell myeloma. Although the therapeutic options may be similar for both POEMS syndrome and myeloma, treatment decisions should be influenced by the consideration that myeloma therapy may carry a higher potential for toxicity in patients with POEMS syndrome [2,18,19].…”

“…Therapeutic approaches differ between limited-and advanced-stage diseases [2,18,19]. In POEMS syndrome, the limited-stage disease describes cases where bone marrow biopsies reveal the absence of clonal plasma cells and only 1-2 lesions are present.…”

“…For patients in this stage, treatment typically includes involved-field radiation therapy at specific doses. Notably, a study conducted at the Mayo Clinic demonstrated that patients with limitedstage disease had a remarkable 4-year overall survival rate of 97% and an event-free survival rate of 52% [2,18,19].…”

“…The pathophysiology of POEMS syndrome is only partly understood. Elevated VEGF levels have emerged as a crucial element, such that VEGF can be used as a diagnostic marker, a means to monitor disease activity, and potentially a therapeutic target [2]. VEGF may play a pivotal role in disrupting the blood-nerve barrier, leading to demyelination and axonal damage, and thereby contributing to the observed neuropathy [3].…”