abt-199 and Skin-Neoplasms

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy that originates from plasmacytoid dendritic cells. It can involve skin, bone marrow, and/or lymph nodes. There is no consensus recommendation regarding treatment especially in the relapsed setting. Tagraxofusp, a CD123 directed agent, was recently approved by the Food and Drug Administration to treat BPDCN. We report a case of an elderly patient with diagnosis of BPDCN who was treated initially with tagraxofusp followed by azacitidine and venetoclax combination on relapse.. Tagraxofusp is a novel therapy that needs more real-world experience. This case describes the clinical course of an elderly patient on tagraxofusp. We also review the literature of azacytidine/venetoclax combination as a potential yet tolerable treatment option for this rare disease entity. This is the fourth case in literature to be treated with this combination.

Topics: Acute Disease; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Bridged Bicyclo Compounds, Heterocyclic; Dendritic Cells; Hematologic Neoplasms; Humans; Male; Recombinant Fusion Proteins; Skin Neoplasms; Sulfonamides

We describe a patient with blastic plasmacytoid dendritic cell neoplasm with central nervous system involvement and the outcome of venetoclax use in this setting.. A 54-year-old Caucasian male was referred to the Haematology Unit with an enlarged inguinal lymph node which was diagnostic of a blastic plasmacytoid dendritic cell neoplasm. The staging revealed disseminated disease (skin, visceral, lymph nodes, and bone marrow). He received chemotherapy with an acute myeloid leukaemia-like regime. Afterwards, he underwent allogeneic haematopoietic stem cell transplantation, though it was not successful, showing a relapse 14 months later with hepatic and central nervous system dissemination. Intrathecal chemotherapy was administered, and venetoclax (anti-bcl2 agent) was started in an off-label indication based on most recent literature. The disease halted its course for 3 months. In the end, the patient's disease progressed and so he succumbed due to infectious complications.. Venetoclax monotherapy seems not enough to control the disease progression under CNS involvement and other treatments should be investigated.

Topics: Bridged Bicyclo Compounds, Heterocyclic; Central Nervous System; Dendritic Cells; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Skin Neoplasms; Sulfonamides

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive subtype of myeloid malignancy characterized by skin, lymph node and central nervous system (CNS) involvement. Although various regimens are used, a standard therapeutic strategy for BPDCN has not been established. Recent studies revealed that BPDCN patients frequently have a mutation in ZRSR2, which is a minor spliceosome component. However, the association between the clinical features of BPDCN and ZRSR2 mutational status remains unknown. A 70-year-old man was referred to our hospital with skin rash and enlarged lymph nodes, as well as blasts in the peripheral blood. BPDCN was diagnosed based on the immunophenotype of the blasts derived from bone marrow. Whole exome sequencing revealed that BPDCN cells collected at diagnosis had mutations in ZRSR2, ZBTB33, CUL3, TET2 and NRAS. RNA sequencing analysis indicated that U12-type intron retention occurred in LZTR1, caused by ZRSR2 loss. After seven cycles of venetoclax combined with azacitidine therapy, BPDCN cells appeared in the peripheral blood and infiltrated the CNS. Two KRAS mutated clones appeared at BPDCN recurrence. These findings are important for understanding the pathogenesis of BPDCN, which will inform development of novel therapeutic strategies.

Topics: Aged; Clonal Evolution; Cullin Proteins; Dendritic Cells; Hematologic Neoplasms; Humans; Male; Ribonucleoproteins; Signal Transduction; Skin Neoplasms; Transcription Factors

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy, especially in pediatrics, that can involve the bone marrow, skin, lymph nodes, and central nervous system (CNS). Given its variable clinical presentation, coupled with an immunohistochemistry pattern (CD4, CD56, TCF4, TCL-1, and CD123 positivity) that differs from other myeloid neoplasms, the diagnosis of BPDCN can be missed. Limited data are available to guide the treatment of pediatric BPDCN. Herein, we report a case of a pediatric patient who had BPDCN with central nervous system, orbital, and skin involvement. This patient achieved complete remission after receiving modified hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone with venetoclax and intrathecal chemotherapy. He remains disease-free 200 days after receiving a stem cell transplant. This represents the first known published pediatric case using a modified hyper-CVAD plus venetoclax regimen for treating a pediatric BPDCN patient in the frontline setting.

Topics: Bridged Bicyclo Compounds, Heterocyclic; Child; Dendritic Cells; Hematologic Neoplasms; Humans; Male; Myeloproliferative Disorders; Skin; Skin Neoplasms

An 84-year-old Japanese man was diagnosed with blastic plasmacytoid dendritic cell neoplasm (BPDCN). We administered combination therapy using venetoclax and azacytidine. We observed neutropenia (Grade 4), thrombocytopenia (Grade 2), and stomatitis (Grade 3). After six cycles of treatment, the BPDCN abnormal cells in the bone marrow specimen almost disappeared, and atypical cells were not detected in a skin biopsy. We propose venetoclax combined with azacytidine as a useful treatment approach in elderly patients, although clinicians should be mindful that therapeutic modifications may be essential to minimize and/or avoid adverse events.

Topics: Aged; Aged, 80 and over; Azacitidine; Dendritic Cells; Humans; Male; Myeloproliferative Disorders; Neutropenia; Skin Neoplasms

Topics: Aged, 80 and over; Azacitidine; Bridged Bicyclo Compounds, Heterocyclic; Dendritic Cells; Female; Humans; Myeloproliferative Disorders; Skin Neoplasms; Sulfonamides

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive primary cutaneous lymphoma characterized by transformed plasmacytoid dendritic cells that overexpress interleukin-3 receptor subunit alpha (IL3RA) also known as CD123. In addition to several therapies currently undergoing clinical trials, Tagraxofusp-erzs (Stemline Therapeutics, Inc., NY) is a single FDA-approved option available for treatment of adults and children over 2 years of age suffering from BPDCN. It was designed to target CD123 overexpression in BPDCN as a CD123-directed cytotoxin consisting of a recombinant human interleukin-3 fused to a truncated diphtheria toxin. We discuss a case of a male patient in his late 70s’ who presented with an asymptomatic rash involving the back and the right knee that initially developed as pink patches, progressed into plaques, and subsequently rapidly evolved into a tumor involving the right knee that was confirmed as BPDCN on skin biopsy and was accompanied by bone marrow involvement. Upon initiation of first line tagraxofusp-erzs therapy, the patient did not achieve improvement. However, off-label use of venetoclax (AbbVie Inc, IL and Genentech-USA, CA), a Bcl2 inhibitor currently in a Phase I clinical trial, resulted in a satisfactory clinical outcome, nearly complete resolution of a right knee tumor lesion, and deferment of bone marrow transplant. We believe that our case exemplifies the complexity of BPDCN, briefly reviews current treatment and management options that are only in their infancy and raises awareness towards success with alternative off-label therapies such as venetoclax when treating BPDCN. J Drugs Dermatol. 20(5):550-551. doi:10.36849/JDD.5373.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Decitabine; Dendritic Cells; Drug Resistance, Neoplasm; Humans; Interleukin-3 Receptor alpha Subunit; Male; Off-Label Use; Proto-Oncogene Proteins c-bcl-2; Recombinant Fusion Proteins; Skin; Skin Neoplasms; Sulfonamides; Treatment Outcome

Topics: Antibodies, Monoclonal; Azacitidine; Bridged Bicyclo Compounds, Heterocyclic; Dendritic Cells; Female; Hematologic Neoplasms; Humans; Skin Neoplasms; Sulfonamides

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Bridged Bicyclo Compounds, Heterocyclic; Dendritic Cells; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Skin Neoplasms; Sulfonamides; Treatment Outcome

Topics: Aged, 80 and over; Bridged Bicyclo Compounds, Heterocyclic; Dendritic Cells; Humans; Male; Myeloproliferative Disorders; Skin Neoplasms; Sulfonamides

Topics: Bridged Bicyclo Compounds, Heterocyclic; Humans; Myeloproliferative Disorders; Skin Neoplasms; Sulfonamides

Topics: Bridged Bicyclo Compounds, Heterocyclic; Humans; Myeloproliferative Disorders; Skin Neoplasms; Sulfonamides

Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Bridged Bicyclo Compounds, Heterocyclic; Dendritic Cells; Female; Hematologic Neoplasms; Humans; Middle Aged; Positron Emission Tomography Computed Tomography; Simvastatin; Skin Neoplasms; Sulfonamides