This site is intended for US Healthcare Professionals only.

Test for CD123: A key marker due to its high expression (~95%) on BPDCN cells3-5

CD123, as part of a signature marker triad with CD4 and CD56, is a key marker in identifying BPDCN—a disease that can be challenging to distinguish from other hematologic malignancies.1,2

Key features of CD123 expression

  • Highly expressed (~95%) on BPDCN cells and negligibly expressed on healthy cells3-6
  • Can be both a diagnostic marker and a therapeutic target in BPDCN4,5,7

*BPDCN diagnosis can include other markers, such as TCL1, TCF4, and CD303 (BDCA2).1,8

BPDCN is a pathologic diagnosis based on immunophenotype analysis through immunohistochemistry or flow cytometry1

Diagnosis of BPDCN requires multiple positive and negative markers1†

Antigens that confirm the diagnosis of BPDCN8-12 Antigens that exclude the diagnosis of BPDCN3,4,9-13 Other markers that may be positive in BPDCN9,10
  • Pan T-cell marker: CD3
  • Pan B-cell markers:
    CD79a, CD20
  • Myeloid markers: CD11c,
    CD163, lysozyme,
    myeloperoxidase
  • Markers of immaturity:
    CD34, CD117
  • CD43
  • TdT
  • CD68
  • CD33

One or more of these markers may be negative in some cases of BPDCN. Negativity does not rule out the diagnosis but does make it less likely.

TdT = terminal deoxynucleotidyl transferase.

Recognizing BPDCN: Morphology

Skin
Punch biopsy of a skin lesion showing BPDCN (H&E stain, x40) and (inset) medium-sized malignant cells spare the epidermis (H&E stain, x1000)14
Bone marrow
Core biopsy showing diffuse infiltrate by BPDCN (H&E stain, x600)14

H&E = hematoxylin and eosin.

Reprinted by permission of SAGE Publications, Inc.

Main morphologic features of BPDCN biopsy

  • Diffuse, monomorphic infiltrate1
  • Medium-sized blast cells with irregular nuclei1,5
  • Fine chromatin5
  • At least 1 small nucleolus5
  • Malignant BPDCN cells do not typically infiltrate the epidermis5

BPDCN with low-density infiltrate may mimic an inflammatory condition5

  • Cutaneous cases with minimal involvement show periadnexal and perivascular infiltrate, clustering in the superficial to mid dermis15,16
  • Cytology, in association with flow cytometry, immunophenotyping, and clinical history, can help obtain an accurate diagnosis of BPDCN17
To help with a timely and accurate diagnosis, consider including CD123, CD4, and CD56 in early diagnostic panels1,2
Explore treatment goals for patients with BPDCN
  1. References:
  2. Pagano L, et al. Blastic plasmacytoid dendritic cell neoplasm: diagnostic criteria and therapeutical approaches. Br J Haematol. 2016;174(2):188-202.
  3. Pemmaraju N, Konopleva M. Treating blastic plasmacytoid dendritic cell neoplasm. The Hematologist website. http://www.hematology.org/Thehematologist/Ask/8927.aspx. Published August 28, 2018. Accessed April 25, 2019.
  4. Pagano L, et al. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study. Haematologica. 2013;98(2):239-246.
  5. Laribi K, et al. Blastic plasmacytoid dendritic cell neoplasm: from origin of the cell to targeted therapies. Biol Blood Marrow Transplant. 2016;22(8): 1357-1367.
  6. Facchetti F, et al. Neoplasms derived from plasmacytoid dendritic cells. Mod Pathol. 2016;29(2):98-111.
  7. Frankel AE, et al. Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients. Blood. 2014;124(3):385-392.
  8. Pemmaraju N. Novel pathways and potential therapeutic strategies for blastic plasmacytoid dendritic cell neoplasm (BPDCN): CD123 and beyond. Curr Hematol Malig Rep. 2017;12(6):510-512.
  9. Ceribelli M, et al. A druggable TCF4- and BRD4-dependent transcriptional network sustains malignancy in blastic plasmacytoid dendritic cell neoplasm. Cancer Cell. 2016;30(5):764-778.
  10. Cronin DM, et al. Immunophenotypic analysis of myeloperoxidase-negative leukemia cutis and blastic plasmacytoid dendritic cell neoplasm. Am J Clin Pathol. 2012;137(3):367-376.
  11. Sangle NA, et al. Optimized immunohistochemical panel to differentiate myeloid sarcoma from blastic plasmacytoid dendritic cell neoplasm. Mod Pathol. 2014;27(8):1137-1143.
  12. Deotare U, et al. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: 10-color flow cytometry diagnosis and HyperCVAD therapy. Am J Hematol. 2016;91(3):283-286.
  13. Garnache-Ottou F, et al. Extended diagnostic criteria for plasmacytoid dendritic cell leukaemia. Br J Haematol. 2009;145(5):624-636.
  14. Pennisi M, et al. A case of blastic plasmacytoid dendritic cell neoplasm extensively studied by flow cytometry and immunohistochemistry. Case Rep Hematol. 2017;2017:4984951. Published March 20, 2017. Accessed October 3, 2018.
  15. Riaz W, et al. Blastic plasmacytoid dendritic cell neoplasm: update on molecular biology, diagnosis, and therapy. Cancer Control. 2014;21(4):279-289.
  16. Reichard KK. Blastic plasmacytoid dendritic cell neoplasm: how do you distinguish it from acute myeloid leukemia? Surg Pathol Clin. 2013;6(4):743-765.
  17. Sullivan JM, Rizzieri DA. Treatment of blastic plasmacytoid dendritic cell neoplasm. Hematology Am Soc Hematol Educ Program. 2016;2016(1):16-23.
  18. Ferreira J, et al. Cytomorphological features of blastic plasmacytoid dendritic cell neoplasm on FNA and cerebrospinal fluid cytology: a review of 6 cases. Cancer Cytopathol. 2016;124(3):196-202.

INDICATION

  • ELZONRIS is a CD123-directed cytotoxin for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older

IMPORTANT SAFETY INFORMATION

Boxed WARNING: CAPILLARY LEAK SYNDROME

  • Capillary Leak Syndrome (CLS), which may be life-threatening or fatal, can occur in patients receiving ELZONRIS. Monitor for signs and symptoms of CLS and take actions as recommended

WARNINGS AND PRECAUTIONS

Capillary Leak Syndrome

  • ELZONRIS can cause capillary leak syndrome (CLS), which may be life-threatening or fatal if not properly managed. The overall incidence of CLS in clinical trials was 55% in patients receiving ELZONRIS, including 46% in Grades 1 or 2, 6% in Grade 3, 1% in Grade 4, and 2 fatal events. Common signs and symptoms (incidence ≥ 20%) associated with CLS that were reported during treatment with ELZONRIS include hypoalbuminemia, edema, weight gain, and hypotension
  • Before initiating therapy with ELZONRIS, ensure that the patient has adequate cardiac function and serum albumin is ≥ 3.2 g/dL
  • During treatment with ELZONRIS, ensure that serum albumin levels are ≥ 3.5 g/dL and have not been reduced by ≥ 0.5 g/dL from the albumin value measured prior to dosing initiation of the current cycle. Monitor serum albumin levels prior to the initiation of each dose or more often as indicated clinically thereafter. Additionally, assess patients for other signs or symptoms of CLS, including weight gain, new onset or worsening edema including pulmonary edema, hypotension, or hemodynamic instability
  • Counsel patients to seek immediate medical attention should signs or symptoms of CLS occur at any time

Hypersensitivity Reactions

  • ELZONRIS can cause severe hypersensitivity reactions. Grade 3 or higher events were reported in 10% of patients in clinical trials. Monitor patients for hypersensitivity reactions during treatment with ELZONRIS. Interrupt ELZONRIS infusion and provide supportive care as needed if a hypersensitivity reaction should occur. If the reaction is severe, discontinue ELZONRIS permanently

Hepatotoxicity

  • Elevations in liver enzymes can occur with ELZONRIS. Grade 3 or higher elevations in liver enzymes occurred in approximately 40% of patients in clinical trials
  • Monitor alanine aminotransferase (ALT) and aspartate aminotransferase (AST) prior to each infusion with ELZONRIS. Temporarily withhold ELZONRIS if the transaminases rise to greater than 5 times the upper limit of normal (ULN) and resume treatment upon normalization or when resolved

ADVERSE REACTIONS:

The most common adverse reactions in the clinical trials (incidence ≥ 30%) are capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight increase. The most common laboratory abnormalities (incidence ≥ 50%) are decreases in albumin, platelets, hemoglobin, calcium, sodium, and increases in glucose, ALT, and AST.

Please see full Prescribing Information, including Boxed WARNING.

To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

IMPORTANT SAFETY INFORMATION

INDICATION

  • ELZONRIS is a CD123-directed cytotoxin for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older

IMPORTANT SAFETY INFORMATION

Boxed WARNING: CAPILLARY LEAK SYNDROME

  • Capillary Leak Syndrome (CLS), which may be life-threatening or fatal, can occur in patients receiving ELZONRIS. Monitor for signs and symptoms of CLS and take actions as recommended

WARNINGS AND PRECAUTIONS

Capillary Leak Syndrome

  • ELZONRIS can cause capillary leak syndrome (CLS), which may be life-threatening or fatal if not properly managed. The overall incidence of CLS in clinical trials was 55% in patients receiving ELZONRIS, including 46% in Grades 1 or 2, 6% in Grade 3, 1% in Grade 4, and 2 fatal events. Common signs and symptoms (incidence ≥ 20%) associated with CLS that were reported during treatment with ELZONRIS include hypoalbuminemia, edema, weight gain, and hypotension
  • Before initiating therapy with ELZONRIS, ensure that the patient has adequate cardiac function and serum albumin is ≥ 3.2 g/dL
  • During treatment with ELZONRIS, ensure that serum albumin levels are ≥ 3.5 g/dL and have not been reduced by ≥ 0.5 g/dL from the albumin value measured prior to dosing initiation of the current cycle. Monitor serum albumin levels prior to the initiation of each dose or more often as indicated clinically thereafter. Additionally, assess patients for other signs or symptoms of CLS, including weight gain, new onset or worsening edema including pulmonary edema, hypotension, or hemodynamic instability
  • Counsel patients to seek immediate medical attention should signs or symptoms of CLS occur at any time

Hypersensitivity Reactions

  • ELZONRIS can cause severe hypersensitivity reactions. Grade 3 or higher events were reported in 10% of patients in clinical trials. Monitor patients for hypersensitivity reactions during treatment with ELZONRIS. Interrupt ELZONRIS infusion and provide supportive care as needed if a hypersensitivity reaction should occur. If the reaction is severe, discontinue ELZONRIS permanently

Hepatotoxicity

  • Elevations in liver enzymes can occur with ELZONRIS. Grade 3 or higher elevations in liver enzymes occurred in approximately 40% of patients in clinical trials
  • Monitor alanine aminotransferase (ALT) and aspartate aminotransferase (AST) prior to each infusion with ELZONRIS. Temporarily withhold ELZONRIS if the transaminases rise to greater than 5 times the upper limit of normal (ULN) and resume treatment upon normalization or when resolved

ADVERSE REACTIONS:

The most common adverse reactions in the clinical trials (incidence ≥ 30%) are capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight increase. The most common laboratory abnormalities (incidence ≥ 50%) are decreases in albumin, platelets, hemoglobin, calcium, sodium, and increases in glucose, ALT, and AST.

Please see full Prescribing Information, including Boxed WARNING.

To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.