Feed

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) has entered a dual CD123-targeted therapy era following the availability of tagraxofusp and the 2026 approval of pivekimab sunirine-pvzy. This development creates a new clinical problem: treatment can no longer be selected solely by distinguishing targeted therapy from conventional chemotherapy; clinicians must choose between mechanistically distinct CD123 platforms while integrating central nervous system (CNS) management, transplantation, comorbidity, organ function, and prior treatment. This narrative review reframes BPDCN around those decisions. It summarizes the minimum diagnostic and staging information needed before therapy; compares tagraxofusp and pivekimab using response, survival, follow-up, and transplant-bridging data; and proposes scenario-based approaches for newly diagnosed, older or frail, transplant-eligible, and relapsed or refractory patients. Tagraxofusp has the longest disease-specific experience and a defined role as remission induction and a bridge to hematopoietic cell transplantation, but capillary leak syndrome requires stringent selection and cycle-1 monitoring. Pivekimab offers a distinct antibody-drug conjugate platform with once-every-3-week dosing and activity in both treatment-naive and relapsed disease, but hepatotoxicity, including hepatic veno-occlusive disease, is a central limitation. Neither agent has established CNS-protective activity. Baseline cerebrospinal fluid assessment and routine prophylactic intrathecal chemotherapy for CSF-negative patients should therefore be distinguished from intensified therapeutic intrathecal treatment for documented CNS involvement. Early donor search, multidimensional response evaluation, and trial enrollment remain integral. The proposed algorithm is evidence-informed rather than guideline-mandated and highlights where prospective studies are most urgently needed.