The role of targeted therapies in blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an ultra-rare disease that arises from malignant precursor dendritic cells. Historically, there was no uniform standard-of-care chemotherapy. In this setting, outcomes were substandard, especially for patients not eligible for intensive chemotherapy, clinical trials, and/or hematopoietic stem cell transplantation, which constituted the majority of patients. The development of targeted therapy, namely the anti-CD123 agent tagraxofusp, marked the beginning of a new era in the treatment of BPDCN.

This review summarizes current targeted therapies in BPDCN, highlights recent therapeutic strategies and emerging approaches with the potential to improve patient outcomes. We also discuss key barriers to clinical implementation, including adverse events associated with anti-CD123-directed therapies and limitations related to treatment cost and accessibility.

The approval of tagraxofusp established a foundation for targeted therapy in BPDCN and demonstrated high response rates, leading to the development of additional antibody - drug conjugates and cellular therapies targeting CD123. Other promising investigational targeted approaches may include BCL2 inhibitors, proteasome inhibitors, and therapies directed against surface antigens such as CD38 and CD303, as well as bromodomain and extraterminal (BET) inhibitors. Collectively, these strategies represent important advances that may significantly improve the historically poor outcomes associated with BPDCN.