Treatment Of Blastic Plasmacytoid Dendritic Cell Neoplasm Research Articles

Blastic plasmacytoid dendritic cell neoplasm (BPDCN): A promising future in the era of targeted therapeutics.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. BPDCN cells characteristically express several markers on their cell surfaces including CD123, CD4, and CD56. Because of its rarity and challenging clinical presentation, there was no standard of care in managing BPDCN for decades and its prognosis overall was poor. However, as understanding of this rare neoplasm has increased, so have treatment options. The conventional cytotoxic chemotherapy regimens once used in the treatment of BPDCN were modest in their impact on disease relapse until paired with hematopoietic stem cell transplant. Although recent data suggest that there still remains a role for chemotherapeutic agents, targeted modalities have expanded the overall BPDCN treatment landscape. The CD123-targeted agent, tagraxofusp, was the first Food and Drug Administration-approved monotherapy in the treatment of BPDCN. Since its inception, several CD123-targeted and other cell-surface agents have been investigated, with many agents still in the preclinical stages. Although relapsed/refractory disease and central nervous system disease both remain formidable areas of research, there are several promising therapeutic approaches that could have a significant impact on the trajectory of treatment. This review will provide detailed insight on the novel drugs currently in use and those being explored in the management of BPDCN.

Outcomes for Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Treated with Frontline HCVAD-Based Chemotherapy

Outcomes for Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Treated with Frontline HCVAD-Based Chemotherapy

Tagraxofusp for the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): A Brief Report on Emerging Data.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy, for which conventional chemotherapy has poor outcomes. CD123, the α-subunit of interleukin (IL)-3 receptor, is constantly overexpressed at the surface of tumoral cells. Tagraxofusp (or SL-401) is a recombinant cytotoxin which consists of human interleukin-3 fused to a truncated diphtheria toxin. It is currently the only novel therapy with a prospective evaluation of efficacy and safety in the treatment of BPDCN and is also the only one to achieve FDA approval. In this short review, the results of tagraxofusp are summarized and perspectives of its use in BPDCN and in other malignancies are discussed. The safety profile is also summarized, since capillary leak syndrome is the main toxic effect of the drug, along with more common toxicities including an increase in transaminases and thrombocytopenia.

Blastic plasmacytoid dendritic cell neoplasm: diagnosis, manifestations, and treatment.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy with historically poor outcomes. It typically manifests as asymptomatic skin lesions and cytopenias, which result from bone marrow involvement. Less commonly, it will present in lymph nodes or visceral organs as well. Although rare, BPDCN has been discussed more frequently in recent years as new drugs have been developed that could be effective at treating this disease. Until recently, treatment for BPDCN commonly included intensive chemotherapy regimens, which are generally reserved for management of acute myeloid leukemia or acute lymphoblastic leukemia. However, in 2018 tagraxofusp (SL-401) was approved as the only treatment specifically indicated for BPDCN. Additional clinical trials are ongoing evaluating the efficacy of newer agents, which could potentially further improve the long-term outcomes for patients with BPDCN. This manuscript reviews the diagnosis, manifestations and treatment of BPDCN.

Enhancer hijacking via disease-specific chromosomal translocation in blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematological malignancy, which seems to originate from the precursor of plasmacytoid dendritic cells. Because BPDCN has an aggressive course and poor prognosis, development of new treatment strategies is essential. Next-Generation Sequencing, a recently evolved technology, reveals new molecular mechanism of BPDCN development. Here I will discuss the recent research on the treatment of BPDCN, including the relationship between chromosomal translocation and enhancer hijacking in BPDCN.

New progression in the therapy of blastic plasmacytoid dendritic cell neoplasms

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a kind of rare and highly invasive hematological malignancy. Because of its low incidence, there is still no consensus on its standard treatment. For young patients, high intensity chemotherapy combined with hematopoietic stem cell transplantation is often used. Elderly patients who cannot accept hematopoietic stem cell transplantation receive low intensity chemotherapy. In December 2018, tagraxofusp, a new targeted drug, was approved by the U. S. Food and Drug Administration specially for treatment-naive and previously-treated BPDCN patients (age≥2 years old). Some targeted drugs, such as venetoclax and daratumumab, have certain effects on the treatment of BPDCN. The efficacies of PD-1/PDL-1 inhibitors and anti CD123 chimeric antigen receptor T cell immunotherapy need further researches. Key words: Hematological neoplasms; Therapy; Blastic plasmacytoid dendritic cell neoplasms

Tagraxofusp, the first CD123-targeted therapy and first targeted treatment for blastic plasmacytoid dendritic cell neoplasm

ABSTRACTIntroduction: CD123 or interleukin 3 receptor alpha is overexpressed in multiple hematologic malignancies. Tagraxofusp is an intravenously administered CD123-directed cytotoxin consisting of the fusion of interleukin-3 with a truncated diphtheria toxin payload and was recently approved by the Food and Drug Administration for the treatment of adults and children aged 2 and older with blastic plasmacytoid dendritic cell neoplasm (BPDCN).Areas Covered: In this review, we discuss the use of tagraxofusp in BPDCN, and active clinical trials involving this agent in several hematologic malignancies are also presented. Tagraxofusp has significant efficacy in patients with BPDCN and manageable safety profile, with the most commonly reported adverse events being asymptomatic elevation of alanine and aspartate aminotransferase levels, hypoalbuminemia, peripheral edema, and thrombocytopenia. The most serious side effect is capillary leak syndrome that can be lethal in some cases but the risk may be mitigated by early recognition and intervention.Expert Opinion: Tagraxofusp has been introduced as a novel treatment of BPDCN, a rare hematologic malignancy, for which no standard therapy previously existed. Many patients treated with this agent were able to be bridged to stem cell transplantation, including older patients. In the future, combinations of tagraxofusp with other targeted agents will be explored.