TY - JOUR
T1 - Recent Advances in the Biology and CD123-Directed Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm
AU - Pemmaraju, Naveen
AU - Deconinck, Eric
AU - Mehta, Priyanka
AU - Walker, Irwin
AU - Herling, Marco
AU - Garnache-Ottou, Francine
AU - Gabarin, Nadia
AU - Campbell, Clinton J.V.
AU - Duell, Johannes
AU - Moshe, Yakir
AU - Mughal, Tariq
AU - Mohty, Mohamad
AU - Angelucci, Emanuele
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2024/4
Y1 - 2024/4
N2 - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive myeloid malignancy of the dendritic cell lineage that affects patients of all ages, though the incidence appears to be highest in patients over the age of 60 years. Diagnosis is based on the presence of plasmacytoid dendritic cell precursors expressing CD123, the interleukin-3 (IL-3) receptor alpha, and a distinct histologic appearance. Timely diagnosis remains a challenge, due to lack of disease awareness and overlapping biologic and clinical features with other hematologic malignancies. Prognosis is poor with a median overall survival of 8 to 14 months, irrespective of disease presentation pattern. Historically, the principal treatment was remission induction therapy followed by a stem cell transplant (SCT) in eligible patients. However, bridging to SCT is often not achieved with induction chemotherapy regimens. The discovery that CD123 is universally expressed in BPDCN and is considered to have a pathogenetic role in its development paved the way for the successful introduction of tagraxofusp, a recombinant human IL-3 fused to a truncated diphtheria toxin payload, as an initial treatment for BPDCN. Tagraxofusp was approved in 2018 by the United States Food and Drug Administration for the treatment of patients aged 2 years and older with newly diagnosed and relapsed/refractory BPDCN, and by the European Medicines Agency in 2021 for first-line treatment of adults. The advent of tagraxofusp has opened a new era of precision oncology in the treatment of BPDCN. Herein, we present an overview of BPDCN biology, its diagnosis, and treatment options, illustrated by clinical cases.
AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive myeloid malignancy of the dendritic cell lineage that affects patients of all ages, though the incidence appears to be highest in patients over the age of 60 years. Diagnosis is based on the presence of plasmacytoid dendritic cell precursors expressing CD123, the interleukin-3 (IL-3) receptor alpha, and a distinct histologic appearance. Timely diagnosis remains a challenge, due to lack of disease awareness and overlapping biologic and clinical features with other hematologic malignancies. Prognosis is poor with a median overall survival of 8 to 14 months, irrespective of disease presentation pattern. Historically, the principal treatment was remission induction therapy followed by a stem cell transplant (SCT) in eligible patients. However, bridging to SCT is often not achieved with induction chemotherapy regimens. The discovery that CD123 is universally expressed in BPDCN and is considered to have a pathogenetic role in its development paved the way for the successful introduction of tagraxofusp, a recombinant human IL-3 fused to a truncated diphtheria toxin payload, as an initial treatment for BPDCN. Tagraxofusp was approved in 2018 by the United States Food and Drug Administration for the treatment of patients aged 2 years and older with newly diagnosed and relapsed/refractory BPDCN, and by the European Medicines Agency in 2021 for first-line treatment of adults. The advent of tagraxofusp has opened a new era of precision oncology in the treatment of BPDCN. Herein, we present an overview of BPDCN biology, its diagnosis, and treatment options, illustrated by clinical cases.
KW - BPDCN
KW - Clinical cases
KW - Myeloid malignancy
KW - Precision oncology
KW - Tagraxofusp
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U2 - 10.1016/j.clml.2023.12.010
DO - 10.1016/j.clml.2023.12.010
M3 - Review article
C2 - 38267355
AN - SCOPUS:85183545284
SN - 2152-2650
VL - 24
SP - e130-e137
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 4
ER -