Challenges and Unmet Needs in Transplant-Ineligible BPDCN Patients

Opinion
Video

Dr. Schiller will discuss the key factors that make the transplant ineligible BPDCN patient population more difficult to treat, the major goals of therapy for these patients, and how the mechanism of action of tagraxofusp suggests potential efficacy in BPDCN.

Case: Management of Elderly Transplant-Ineligible BPDCN Patients

Clinical Presentation:

  • A 74-year-old lady presents with fatigue, bruising like lesion on upper chest, and shortness of breath that had been present for around 6 months.

Initial Clinical Workup and Diagnosis:

  • Initially suspected to have acute myeloid leukemia (AML) based on preliminary workup at a community oncology clinic.
  • Referred to academic cancer center for further evaluation after not responding well to initial AML treatment.
  • PMH: Hypertension, Type II Diabetes, H/O MI in 2015
  • PE: Notable for pallor, petechiae, and no lymphadenopathy or hepatosplenomegaly
  • ECOG PS =2
  • Labs: WBC 5 x 10 K/uL, Hb 7.8 g/dL, platelets 25x 109 /L.
  • Peripheral smear shows 70% blasts.
  • Bone marrow biopsy showed numerous immature cells felt to represent acute leukemia.
  • Cytogenetics: Complex karyotype
  • LDH elevated at 1200 u/L
  • Lives in assisted living facility, requires assistance with activities of daily living.
  • No available matched sibling or unrelated donor identified.
  • Upon referral to the academic center, pathology was reviewed, and additional material assessed leading to diagnoses of BPDCN.

Initial Treatments:

  • Patient was initiated on:
    • Standard-dose cytarabine 150 mg/m2 continuous infusion x 7 days with idarubicin 12 mg/m2 or daunorubicin 60–90 mg/m2 x 3 days10
  • After failure to achieve remission, she received:
    • Tagraxofusp 12 mcg/kg IV over 15 minutes once daily on days 1–5 of a 21-day cycle

This is a synopsis of a Case-Based Peer Perspectives series featuring Gary Schiller, MD, of UCLA David Geffen School of Medicine.

Gary Schiller, MD, Chief of the Hematology Stem Cell Transplant Program at David Geffen School of Medicine, UCLA, discussed the characteristics and treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN). Dr. Schiller explained that BPDCN was identified as a distinct entity in 2016 and was previously referred to as blastic NK leukemia or a subset of acute myeloid leukemia (AML). In 2022, the World Health Organization classified BPDCN as a neoplasm of dendritic cell and histiocyte origin, distinct from AML.

According to Dr. Schiller, BPDCN typically presents in patients in their 60s or 70s, with a male predominance. Some patients may have a history of hematologic malignancies, such as myelodysplastic syndrome, acute leukemia, or chronic myelomonocytic leukemia. BPDCN involves the bone marrow, skin, lymph nodes, and central nervous system, requiring awareness from hematologists, oncologists, and dermatologists for accurate diagnosis.

Dr. Schiller emphasized the importance of using a broad panel of markers in pathology to identify the expression pattern of the neoplastic cells. Patients typically present with progressive pancytopenia and at least one cutaneous lesion, which may be confused with ecchymotic lesions, Kaposi sarcoma, or extramedullary involvement of other acute leukemias. The diagnostic workup includes bone marrow morphology, flow cytometry, immunohistochemistry, skin biopsy, cytogenetics, and molecular analysis. Common molecular abnormalities in BPDCN include mutations in ASXL1, TET1, TET2, IDH1, IDH2, NRAS, TP53, and ZRSR2.

Regarding treatment, Dr. Schiller discussed the mechanism of action of tagraxofusp, a CD123-targeted therapy. Tagraxofusp consists of human interleukin-3 (IL-3) fused to a truncated diphtheria toxin payload, which binds to the IL-3 receptor (CD123) and induces apoptosis of the cell. Tagraxofusp has been included in the National Comprehensive Cancer Network (NCCN) guidelines and remains the only approved drug for the management of BPDCN, although other drugs are in development.

*Video synopsis is AI-generated and reviewed by Targeted Oncology editorial staff.

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