Two-Year Clinical Outcomes in a Challenging Case of POEMS Syndrome with an Atypical Presentation

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is a rare plasma cell disorder with multisystem involvement and recognized neuro-ophthalmic manifestations, including papilledema. We report two-year outcomes of daratumumab, lenalidomide, and dexamethasone (DRd) as first-line therapy in a 64-year-old man who presented with bilateral optic disc edema and progressive neuropathic symptoms. Initial electrophysiologic studies and serum protein electrophoresis were unrevealing. With clinical progression, repeat testing demonstrated severe demyelinating polyneuropathy, markedly elevated vascular endothelial growth factor (VEGF), and increased serum free light chains, establishing the diagnosis of POEMS syndrome. Treatment with DRd resulted in rapid clinical improvement, substantial reduction in VEGF levels, resolution of papilledema with normalization of retinal nerve fiber layer thickness on optical coherence tomography, and sustained remission over two years of follow-up. This case emphasizes the importance of continued diagnostic reassessment when early studies are unrevealing and documents durable systemic and neuro-ophthalmic improvement with DRd.