Tagraxofusp in adult blastic plasmacytoid dendritic cell neoplasm: clinical trials and real-world outcomes: a systematic review.

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic malignancy. Tagraxofusp, a CD123-directed cytotoxin, was approved based on phase I/II data, and subsequent studies have expanded evidence across trial and real-world settings. Methods: We systematically searched PubMed, Scopus, and Google Scholar for English-language human studies through January 25, 2026. We included adults (≥18 years) with BPDCN treated with tagraxofusp who reported efficacy and/or safety outcomes; abstracts without extractable data, narrative reviews, expert guidance, pediatric-only studies, and preclinical studies were excluded. Results: Twenty-seven studies were included, representing 343 unique adult patients treated with tagraxofusp after adjustment for overlapping analyses from the pivotal NCT02113982 trial program. Frontline trials reported overall response rates (ORR) of 71%-90% with CR/CRc rates of 56%-72%. Real-world cohorts showed ORR of 65%-90% and highlighted superior survival among patients bridged to allogeneic hematopoietic stem cell transplantation (HSCT). Capillary leak syndrome (CLS) was the defining toxicity, with variable incidence across clinical trials and observational cohorts. Conclusions: Tagraxofusp demonstrates consistent remission-inducing activity in adults with BPDCN across prospective and real-world settings. Long-term survival appears strongly influenced by successful bridging to HSCT. Evidence remains predominantly non-randomized, underscoring the need for comparative and combination studies.