Chemotherapy Options for Blastic Plasmacytoid Dendritic Cell Neoplasm

Haddadin, Michael; Taylor, Justin

doi:10.1016/j.hoc.2020.01.011

Cited by 12 publications

(6 citation statements)

References 84 publications

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“…5 Patients diagnosed with this disease have been historically treated with systemic chemotherapy regimens used in the management of other acute leukemias. 6 Chemotherapeutic agents have demonstrated varying levels of benefit in achieving sustained clinical response in patients with BPDCN. 7 However, with the revelation of overexpressed cell-surface markers in BPDCN such as CD123 and overexpression of BCL2, targeted therapies have now been added to both frontline and relapsed/refractory treatment options.…”

Section: Introductionmentioning

confidence: 99%

“…Given both its rarity and the prior paucity of information regarding its lineage, BPDCN had no therapies considered standard of care until recently 5 . Patients diagnosed with this disease have been historically treated with systemic chemotherapy regimens used in the management of other acute leukemias 6 . Chemotherapeutic agents have demonstrated varying levels of benefit in achieving sustained clinical response in patients with BPDCN 7 .…”

Section: Introductionmentioning

confidence: 99%

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

Adimora

Wilson

Pemmaraju

2022

Cancer

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Adimora

Wilson

Pemmaraju

2022

Cancer

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“…Prior to the approval of tagraxofusp, treatment of BPDCN involved applying a multiagent chemotherapy regimen developed for AML, acute lymphoblastic leukemia (ALL) or lymphoma. [7][8][9][10] Even patients who present with more indolent "skin-only" disease should be offered systemic therapy. In the absence of systemic treatment, the disease invariably advances to a leukemic or lymphomatous phase, although the time to progression is variable.…”

Section: Treatment Of Bpdcn With Chemotherapymentioning

confidence: 99%

“…However, retrospective studies suggest that acute leukemia regimens, particularly ALL regimens, have superior efficacy. [9][10][11] Despite this, chemotherapy-treated patients fare poorly due to inherently aggressive, chemo-resistant disease biology combined with an older patient demographic precluding many from receiving optimal treatment intensity. As with older adults treated for AML and ALL, older patients with BPDCN experience high early mortality, modest remission rates (~50%), and a median overall survival (OS) of less than 2 years due to early treatment failure (refractory disease, early mortality), relapses, and deaths in remission from regimen-related toxicity.…”

Section: Treatment Of Bpdcn With Chemotherapymentioning

confidence: 99%

Tagraxofusp for blastic plasmacytoid dendritic cell neoplasm

Luskin

Lane

2023

haematol

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that presents with characteristic dark purple skin papules, plaques, and tumors, but may also involve the bone marrow, blood, lymph nodes, and central nervous system. The disease, which commonly affects older men but can also present in children, is associated with a distinct immunophenotype including universal expression of CD123, the alpha chain of the interleukin 3 receptor. Recently, tagraxofusp, a CD123-targeting drug consisting of the ligand for CD123, interleukin 3, conjugated to a truncated diphtheria toxin payload was approved for treatment of BPDCN. This was the first agent specifically approved for BPDCN and the first CD123 targeted agent in oncology. Here, we review the development of tagraxofusp and the key preclinical insights and clinical data that led to approval. Tagraxofusp treatment is associated with a unique toxicity, capillary leak syndrome (CLS), which can be severe but is manageable with proper patient selection and monitoring, early recognition, and directed intervention. We outline our approach to the use of tagraxofusp and discuss open questions in treatment of BPDCN. Overall, tagraxofusp represents a unique targeted therapy and a step forward in meeting an unmet need for patients with this rare disease.

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“…BPDCN is generally characterized by CD123+, CD4+, CD56+ expression, as well as CD303 5 , TCL-1 and TCF4 6 , which has also led to treatment implications with identification of novel therapeutic targets 7,8 . Prior to the development of targeted agents against CD123, BPDCN was treated either with local surgical or radiation therapy for cutaneous-limited disease 9,10 , or with multi-agent cytotoxic chemotherapy regimens adopted from use in other hematologic malignancies such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and lymphoma [11][12][13] . Without subsequent hematopoietic stem cell transplantation (HSCT), development of relapsed and refractory disease that is resistant to chemotherapy is high, with poor prognosis and median survival of less than two years 2 .…”

mentioning

confidence: 99%

Characteristics and outcomes of patients with blastic plasmacytoid dendritic cell neoplasm treated with frontline HCVAD

et al. 2022

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive blood cancer, often involving skin, bone marrow, lymph nodes, as well as central nervous system (CNS) involvement in 20-30% of patients. Despite significant progress in CD123- and BCL-2-targeted therapy, most patients are not cured outside of hematopoietic stem cell transplant (HSCT), and CNS relapses are being observed quite frequently. Combination approaches with both targeted and chemotherapy agents plus incorporation of prophylactic CNS-directed therapy are urgently needed. In this setting, we sought to analyze outcomes of the cytotoxic chemotherapy backbone regimen hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone (HCVAD) in BPDCN. We conducted a retrospective analysis of patients with BPDCN (n=100), evaluating complete remission (CR) and median overall survival (OS) among three groups: those who received frontline HCVAD-based (n=35) vs SL-401 (n=37) vs other regimens (n=28). HCVAD-based regimens yielded higher CR (80% vs 59% vs 43%, p=0.01). There was no significant difference in OS (28.3 vs 13.7 vs 22.8 months p=0.41), nor significant difference in remission duration probability among treatment groups (38.6 vs NR vs 10.2 months; p=0.24). HSCT was performed in 51% vs 49% vs 38% respectively (p=0.455). These results suggest a continued important role for HCVAD-based chemotherapy for BPDCN, even in the modern targeted-therapy era, with high CR rates in the frontline setting. Further studies must establish the clinical activity, feasibility, and safety, of doublet/triplet combinations of targeted therapies plus cytotoxic agents and addition of CNS prophylaxis, with ultimate goal of durable long-term remissions for patients with BPDCN.

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Chemotherapy Options for Blastic Plasmacytoid Dendritic Cell Neoplasm

Cited by 12 publications

References 84 publications

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

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

Tagraxofusp for blastic plasmacytoid dendritic cell neoplasm

Characteristics and outcomes of patients with blastic plasmacytoid dendritic cell neoplasm treated with frontline HCVAD

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