Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy arising from precursor plasmacytoid dendritic cells. It accounts for less than 1% of all hematologic cancers, making its diagnosis and management particularly challenging. BPDCN is characterized by a unique immunophenotype, typically expressing CD4, CD56, and plasmacytoid dendritic cell markers such as CD123 (IL-3 receptor α), TCL1, and BDCA-2.

 

BPDCN often presents with cutaneous lesions as the initial manifestation, which may appear as nodules, plaques, or bruise-like discolorations. In many cases, these lesions are accompanied by systemic involvement, including bone marrow infiltration, lymphadenopathy, and splenomegaly. Without treatment, BPDCN progresses rapidly, and the prognosis is poor, with median survival historically ranging from 8 to 14 months.

Elzonris (tagraxofusp-erzs) is a first-in-class targeted therapy approved by the FDA for the treatment of BPDCN in adults and pediatric patients aged two years and older. This novel agent is a CD123-directed cytotoxin composed of a recombinant fusion protein combining interleukin-3 (IL-3) with a truncated diphtheria toxin. It selectively binds to CD123, a hallmark marker overexpressed in BPDCN, delivering the diphtheria toxin directly into malignant cells to induce apoptosis.

 

Clinical trials demonstrated the efficacy of Elzonris in both treatment-naïve and relapsed/refractory BPDCN. In a pivotal trial, the drug achieved a high overall response rate (ORR), including complete response (CR) in a significant proportion of patients, particularly in those treated during earlier disease stages. Despite its promise, Elzonris requires careful administration due to potential toxicities, including capillary leak syndrome (CLS), which can be life-threatening without prompt recognition and management.

 

Elzonris represents a significant advancement in the treatment of BPDCN, offering a targeted approach for a disease with limited therapeutic options. Ongoing research is exploring its use in combination with other therapies and its potential applications in other CD123-positive malignancies.