Novel Therapeutic Approaches in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Era of Targeted Therapy

Wilson, Nathaniel; Konopleva, Marina; Khoury, Joseph D.; Pemmaraju, Naveen

doi:10.1016/j.clml.2021.05.018

Cited by 24 publications

(34 citation statements)

References 107 publications

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“…BPDCN cells are usually positive for CD4, CD56, CD123, TCL-1, and TCF-4 and negative for lineage-specific markers for B-cells, T-cells, and myeloid cells [ 1 ]. Despite initial response to chemotherapy, most patients develop early relapse with median overall survival of about one year [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Integrated Clinical Genotype-Phenotype Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm

Yin

Pemmaraju

You

et al. 2021

Cancers

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive neoplasm derived from plasmacytoid dendritic cells. While advances in understanding the pathophysiology of the disease have been made, integrated systematic analyses of the spectrum of immunophenotypic and molecular alterations in real-world clinical cases remain limited. We performed mutation profiling of 50 BPDCN cases and assessed our findings in the context of disease immunophenotype, cytogenetics, and clinical characteristics. Patients included 42 men and 8 women, with a median age of 68 years (range, 14–84) at diagnosis. Forty-two (84%) patients had at least one mutation, and 23 (46%) patients had ≥3 mutations. The most common mutations involved TET2 and ASXL1, detected in 28 (56%) and 23 (46%) patients, respectively. Co-existing TET2 and ASXL1 mutations were present in 17 (34%) patients. Other recurrent mutations included ZRSR2 (16%), ETV6 (13%), DNMT3A (10%), NRAS (10%), IKZF1 (9%), SRSF2 (9%), IDH2 (8%), JAK2 (6%), KRAS (4%), NOTCH1 (4%), and TP53 (4%). We also identified mutations that have not been reported previously, including ETNK1, HNRNPK, HRAS, KDM6A, RAD21, SF3A1, and SH2B3. All patients received chemotherapy, and 20 patients additionally received stem cell transplantation. With a median follow-up of 10.5 months (range, 1–71), 21 patients achieved complete remission, 4 had persistent disease, and 24 died. Patients younger than 65 years had longer overall survival compared to those who were ≥65 years (p = 0.0022). Patients who had ≥3 mutations or mutations in the DNA methylation pathway genes had shorter overall survival (p = 0.0119 and p = 0.0126, respectively). Stem cell transplantation significantly prolonged overall survival regardless of mutation status. In conclusion, the majority of patients with BPDCN have somatic mutations involving epigenetic regulators and RNA splicing factors, in addition to ETV6 and IKZF1, which are also frequently mutated. Older age, multiple mutations, and mutations in the DNA methylation pathway are poor prognostic factors.

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Section: Introductionmentioning

confidence: 99%

Integrated Clinical Genotype-Phenotype Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm

Yin

Pemmaraju

You

et al. 2021

Cancers

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“…5 In addition, clinical trials with venetoclax (BCL2 inhibitor), tagraxofusp, and other CD123targeted therapies and combinations of these agents with chemotherapy are still ongoing. 3 In conclusion, it should be kept in mind that many systemic diseases including hematologic malignancies may present with skin lesions. BPDCN is a rare disease with an aggressive course and high recurrence risk.…”

Section: Discussionmentioning

confidence: 99%

“…5 In addition, clinical trials with venetoclax (BCL2 inhibitor), tagraxofusp, and other CD123-targeted therapies and combinations of these agents with chemotherapy are still ongoing. 3…”

Section: Discussionmentioning

confidence: 99%

“…The disease has an aggressive nature, and although patients achieve a CR rate of .60% after initial treatment, most patients relapse within 2 years. 3 The most effective treatment option with survival benefit is ASCT performed in first CR. 2,4 In the light of these data, we started hyper-CVAD chemotherapy for our patient and consolidated this treatment with ASCT.…”

Section: Discussionmentioning

confidence: 99%

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A Rare and Aggressive Disease: Answer

Sönmez

Küçükyurt

Men

et al. 2022

The American Journal of Dermatopathology

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN). CLINICAL OUTCOMEA positron emission tomography/computed tomography scan showed widespread cutaneous and subcutaneous lesions throughout the body and lymph nodes in the bilateral axilla, more prominent on the left side. The bone marrow biopsy did not reveal disease infiltration.Hyper-CVAD therapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine) was started. After cycle 1, the skin lesions disappeared completely (Fig. 1H). Complete response (CR) was obtained in positron emission tomography/computed tomography after 2 cycles. Then, he underwent an allogeneic stem-cell transplantation (ASCT) from his human leukocyte antigen-matched sibling donor using myeloablative conditioning regimen with busulfan and cyclophosphamide in September 2021. Cyclosporine and methotrexate were used for the graftversus-host disease prophylaxis. On day +35, the chimerism was 100% in the peripheral blood with no signs for graftversus-host disease.

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“… 32 , 33 Other active clinical trial approaches in the R/R setting include Chimeric Antigen Receptor (CAR-T) therapy, bispecific molecules, immunotherapy approaches, and combination therapy approaches including hypomethylating agents, and BCL2 antagonists (venetoclax), and cytotoxic chemotherapy regimens not yet used in the frontline approach. 34 …”

Section: Unmet Clinical Needsmentioning

confidence: 99%

Unmet Clinical Needs and Management Recommendations for Blastic Plasmacytoid Dendritic Cell Neoplasm: A Consensus-based Position Paper From an Ad Hoc International Expert Panel

et al. 2023

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematological malignancy characterized by recurrent skin nodules, an aggressive clinical course with rapid involvement of hematological organs, and a poor prognosis with overall survival. The rarity of the disease results in a few large-scale studies, a lack of controlled clinical trials for its management, and a lack of evidence-based guidelines. Here, we present a review of unmet clinical needs on the management of BPDCN by a panel of eleven experts involved in the research and clinical practice of BPDCN. Recommendations and proposals were achieved by multiple-step formalized procedures to reach a consensus after a comprehensive analysis of the scientific literature. The panel analyzed the critical issues of diagnostic pathway, prognostic stratification, therapy for young and fit patients and elderly and unfit patients, indication for allotransplant and for autotransplant, indication for central nervous system prophylaxis, and management of pediatric BPDCN patients. For each of these issues, consensus opinions were provided and, when appropriate, proposals for advancement in clinical practice were addressed. The hope is that this comprehensive overview will serve to improve the practice of BPDCN and inform the design and implementation of new studies in the field.

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Novel Therapeutic Approaches in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Era of Targeted Therapy

Cited by 24 publications

References 107 publications

Integrated Clinical Genotype-Phenotype Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm

Integrated Clinical Genotype-Phenotype Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm

A Rare and Aggressive Disease: Answer

Unmet Clinical Needs and Management Recommendations for Blastic Plasmacytoid Dendritic Cell Neoplasm: A Consensus-based Position Paper From an Ad Hoc International Expert Panel

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