The role of targeted therapies in blastic plasmacytoid dendritic cell neoplasm

TY - JOUR

T1 - The role of targeted therapies in blastic plasmacytoid dendritic cell neoplasm

AU - Azevedo, Roberta S.

AU - Nooruddin, Zohra

AU - Bhatia, Sumeet

AU - Finn, Laura

AU - Davis, Carter

AU - Alsfeld, Leonard C.

AU - Subbiah, Suki

AU - Norkin, Maxim

AU - Ulrickson, Matthew

AU - De La Fuente, Adolfo

AU - Larson, Melissa L.

AU - Budak-Alpdogan, Tulin

AU - Pemmaraju, Naveen

N1 - Publisher Copyright: © 2025 Informa UK Limited, trading as Taylor & Francis Group.

PY - 2026

Y1 - 2026

N2 - Introduction: 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. Areas covered: 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. Expert opinion: 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.

AB - Introduction: 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. Areas covered: 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. Expert opinion: 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.

UR - https://www.scopus.com/pages/publications/105027810398

UR - https://www.scopus.com/pages/publications/105027810398#tab=citedBy

U2 - 10.1080/14712598.2025.2610291

DO - 10.1080/14712598.2025.2610291

M3 - Review article

C2 - 41447337

SN - 1471-2598

VL - 26

SP - 15

EP - 24

JO - Expert Opinion on Biological Therapy

JF - Expert Opinion on Biological Therapy

IS - 1

ER -