Treatment Considerations for Fit Elderly BPDCN Patients

EP: 1.Clinical Presentation and Diagnosis of BPDCN

EP: 2.Challenges and Unmet Needs in Transplant-Ineligible BPDCN Patients

EP: 3.Current Therapies and Strategies for Transplant-Ineligible BPDCN Patients

EP: 4.Improving BPDCN Recognition and Diagnosis

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EP: 5.Treatment Considerations for Fit Elderly BPDCN Patients

EP: 6.Future Landscape of BPDCN Management

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 treatment options for a 74-year-old patient with well-controlled diabetes and an excellent performance status diagnosed with blastic plasmacytoid dendritic cell neoplasm (BPDCN). Dr. Schiller noted that allogeneic transplant is not off the table for this patient, but the method of achieving remission depends on the physician's preferences.

Dr. Schiller expressed his preference for using a CD123-directed approach, such as tagraxofusp, to achieve remission, as he believes the response is far more likely with this approach compared to alternatives like hypomethylating agents and venetoclax. However, he acknowledged that some listeners might disagree with this opinion.

Regarding the timing of CD123-directed therapy, Dr. Schiller stated that he does not see a need to delay its use for consolidation, as this was not how the drug was tested or approved. While he understands the rationale for using an alternative induction regimen, such as a hypomethylating agent and venetoclax, followed by tagraxofusp to decrease the risk of capillary leak syndrome, this approach does not align with the drug's approved use.

Once the patient achieves remission, Dr. Schiller would consider transplantation if a suitable fully histocompatible donor were identified. However, if the patient must rely on a haploidentical donor, he expressed concern about the long-term efficacy, as the main issue with BPDCN is late relapse. Dr. Schiller noted that there is insufficient data to provide guidance on using alternative donors with post-transplant cyclophosphamide, given the higher risk of relapse.

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