Severe hypereosinophilia and eosinophilic myocarditis during secondary plasma cell leukemia: evidence of a paraneoplastic manifestation of aggressive myeloma evolution.

Secondary plasma cell leukemia (sPCL) represents one of the most aggressive forms of Multiple Myeloma (MM) progression and remains associated with poor outcomes despite the availability of novel immunotherapeutic approaches. Severe hypereosinophilia is exceptionally rare in plasma cell neoplasms and may occasionally occur as a paraneoplastic manifestation of aggressive disease biology. In selected cases, eosinophilic infiltration can result in life-threatening organ damage, particularly involving the cardiovascular system. We report the case of a 40-year-old woman with IgG lambda MM who achieved complete remission following daratumumab-based induction therapy, autologous stem cell transplantation, and lenalidomide maintenance. Approximately one year after transplantation, she developed rapidly progressive relapse characterized by constitutional symptoms, circulating clonal plasma cells, extensive bone marrow involvement, severe hypereosinophilia, and marked cardiac biomarker elevation. Comprehensive infectious, autoimmune, and molecular investigations excluded alternative causes of eosinophilia. Cardiac magnetic resonance imaging revealed diffuse myocardial edema, increased myocardial wall thickness, extensive subendocardial late gadolinium enhancement, regional wall motion abnormalities, and left ventricular mural thrombosis, findings highly suggestive of eosinophilic myocarditis with endomyocardial involvement consistent with Loeffler syndrome. Urgent cytoreductive therapy with cyclophosphamide and dexamethasone resulted in rapid normalization of eosinophil counts, substantial clinical improvement, and reduction of cardiac symptoms, strongly supporting a pathogenetic relationship between eosinophilia and plasma cell disease burden. Despite subsequent salvage therapies, including isatuximab-based treatment and the BCMA-directed bispecific antibody elranatamab, disease control remained transient and the patient ultimately died from refractory sPCL. This case highlights severe hypereosinophilia as a rare paraneoplastic manifestation of aggressive clonal evolution in MM and emphasizes the importance of prompt recognition of eosinophilic cardiac involvement. The close correlation between eosinophil kinetics and disease activity further suggests that hypereosinophilia may represent a potential clinical indicator of aggressive plasma cell disease evolution and warrants further investigation.