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

Abstract

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.

Incidence, prognostic factors, and survival outcomes in patients with blastic plasmacytoid dendritic cell neoplasm: A retrospective study in the Surveillance, Epidemiology, and End Results database

“…1,5,10,11,13,14,16 However, the median age at diagnosis was 31 years in our study, which is inconsistent with previous studies. 1,[10][11][12][13][14]29 One possible cause of this phenomenon is the bimodal incidence pattern of BPDCN. As shown in our study, 261 of 697 (37.45%) were under the age of 20 years.…”

“…10 According to most literature reports, the median age at diagnosis is 60-70 years, and the majority of patients are male. 1,[10][11][12][13][14] BPDCN usually manifests as infiltration of multiple organs, including the cutaneous system, bone marrow, lymph nodes, central nervous system, and other extranodal organs, and its clinical symptoms differ according to the locations of involvement. 11,15 However, skin lesions are often the first sign.…”

“…There is no exact estimate of the incidence of BPDCN, although it has been reported to represent 0.5% of all hematologic malignancies 10 . According to most literature reports, the median age at diagnosis is 60–70 years, and the majority of patients are male 1,10–14 . BPDCN usually manifests as infiltration of multiple organs, including the cutaneous system, bone marrow, lymph nodes, central nervous system, and other extranodal organs, and its clinical symptoms differ according to the locations of involvement 11,15 .…”

Leukemia cutis in T-cell acute lymphoblastic leukemia: a 3-year follow-up case report

“…Additionally, as our patient presented with skin lesions as the initial symptom and the lymph nodes and bone marrow were subsequently found to be involved, other tumors with similar manifestations-such as blastic plasmacytoid dendritic cell neoplasm-should be excluded. The tumor cells in blastic plasmacytoid dendritic cell neoplasm are usually monomorphic, poorly differentiated, and intermediate-sized blasts with fine chromatin, which most importantly express CD4, CD56, and CD123 (7).…”

Venetoclax and Azacitidine in the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm Refractory to Conventional Therapy

“…Given the reduction in white blood cell count and hemoglobin following Ven/Aza therapy in our patient, he will need regular monitoring with weekly cycles of chemotherapy. Trials investigating the effects of venetoclax either as a single agent (NCT03485547) or in combination with tagraxofusp (NCT03113643) are ongoing [ 15 - 16 ].…”