An update on the diagnosis and management of the polyneuropathy of POEMS syndrome

Abstract

POEMS syndrome is a rare, chronic, disabling paraneoplastic disorder characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells disorder and skin changes. Diagnosis relies on the fulfillment of a set of clinical criteria of which polyneuropathy and a monoclonal plasma cell dyscrasia are early and essential features. Treatment may be either local or systemic and is aimed at the monoclonal plasma cell disorder. Our knowledge of the pathogenesis underlying the POEMS syndrome has advanced greatly over the past years, favoring an important progression in the recognition and management of this disorder. Here, we discuss the recent literature that has advanced our knowledge of the pathogenesis and clinical management of the polyneuropathy in POEMS syndrome.

From pathogenesis to personalized treatments of neuropathies in hematological malignancies

“…Polyneuropathy and the monoclonal gammopathy (lambda‐restricted in the majority of cases) are the hallmark of the disease and the mandatory criteria, but a wide range of clinical features contribute to the syndrome, among which pulmonary hypertension, papilledema, extravascular volume overload (peripheral edema, pleural and pericardial effusions, ascites), withe nails, thrombocytosis, ischemic stroke, and Castleman's disease 34,35 . The diagnosis relies on a set of clinical criteria of which polyneuropathy and a monoclonal plasma cell dyscrasia are early and mandatory features 36 …”

“…Despite the relationship between response to treatment and dropping levels of VEGF, the most successful therapy acts against plasma cells rather than solely targeting VEGF with anti‐VEGF antibodies 34‐36 . Radiotherapy has been shown to be highly active in the subset of patients with an isolated bone lesion and without clonal plasma cells on bone marrow biopsy 47 .…”

“…Instead, when there is a disseminated bone marrow involvement even with a low plasma cell count treatment is borrowed by multiple myeloma and/or AL amyloidosis 34‐36 . The current gold standard treatments for POEMS syndrome rely either on low dose or high dose melphalan‐based conditioning chemotherapy followed by autologous stem cell transplantation, that showed good hematologic control (more than 80% of hematological remissions 48 ), and neurological response with clinical and also neurophysiological improvement of neuropathy in almost all patients, and good survival 33‐46‐48 . The immunomodulating and anti‐angiogenetic agent lenalidomide showed encouraging results either in treatment naive and relapsed patients 49‐51 .…”

“…The immunomodulating and anti‐angiogenetic agent lenalidomide showed encouraging results either in treatment naive and relapsed patients 49‐51 . While most patients respond to lenalidomide, relapses invariably occur 3 to 10 months after the end of therapy 36 . Activity of bortezomib, the first in class proteasome inhibitor, has been reported in approximately 50 cases 33‐52‐53 .…”

“…The BCR and CD20 play a key role in the pathogenesis of CLL as exemplified by the high efficacy of BTK inhibitors, such as ibrutinib, and obinutuzumab, a glycoengineered anti‐CD20 monoclonal antibody 56 . Peripheral neuropathy in CLL may be due to different causes, as among which viral infections (varicella zoster virus, VZV; hepatitis C virus, HCV), iatrogenic (ibrutinib, lenalidomide), immune‐mediated, rarely neuropathy is secondary to invasion by leukemic cells 29‐64 or light chain amyloidosis 65 . In a single centre cohort of more than 800 CLL patients, we identified 19 (2.2%) subjects who developed neuropathy during the follow‐up, with an estimated incidence by time to neuropathy development of 2.1% and 6.9% after 10 and 20 years from the CLL diagnosis, respectively 29 .…”