An atypical POEMS-like paraneoplastic syndrome associated with IgA κ smoldering multiple myeloma treated with daratumumab

POEMS syndrome is a rare paraneoplastic disorder driven by an underlying plasma cell dyscrasia and characterized by polyneuropathy with multisystem features. Although most cases are associated with lambda light chains, kappa-restricted disease is uncommon. We report a woman with IgA kappa smoldering multiple myeloma who presented with long-standing, progressive sensorimotor neuropathy and systemic features including lymphadenopathy and cutaneous changes. Bone marrow biopsy demonstrated 10% kappa-restricted plasma cells with trisomy 5 and trisomy 9. She was started on daratumumab, lenalidomide, and dexamethasone; lenalidomide was discontinued after the first cycle due to hypersensitivity, and therapy continued with daratumumab plus dexamethasone for six total cycles. Treatment resulted in a very good partial response, with marked reduction of the IgA monoclonal protein, improvement in free light-chain ratio, and decreased marrow plasma cells to 5%. Clinically, neuropathy and functional symptoms improved within several months of cytoreduction. This case underscores an atypical kappa-restricted variant of POEMS syndrome and supports the role of CD38-directed therapy as an effective and well-tolerated option in plasma cell–mediated paraneoplastic disease. Early recognition of POEMS features in the setting of a small plasma cell clone can facilitate timely plasma cell–directed therapy and meaningful neurologic recovery.