What is the recommended treatment approach for lung involvement in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)?

Treatment Approach for Lung Involvement in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

For patients with BPDCN with lung involvement, the recommended treatment approach is a clinical trial (preferred) or tagraxofusp-erzs, followed by consideration for allogeneic or autologous hematopoietic cell transplantation (HCT) if complete remission is achieved. 1

Diagnostic Confirmation

Before initiating treatment for lung involvement in BPDCN:

• Confirm diagnosis with immunophenotyping showing expression of at least 4 of these 6 antigens: CD123, CD4, CD56, TCL-1, CD2AP, and CD303/BDCA-2 2
• Perform PET/CT scan to evaluate extent of extramedullary disease including lung involvement 1, 2
• Evaluate for CNS disease with lumbar puncture 2

Treatment Algorithm for BPDCN with Lung Involvement

First-line Treatment Options (in order of preference):

1. Clinical trial (preferred) 1
2. Tagraxofusp-erzs 1
   • Requires serum albumin ≥3.2 g/dL
   • Replace serum albumin if <3.5 g/dL or if reduced by ≥0.5 g/dL from baseline
   • Premedicate with H1-histamine antagonist, acetaminophen, corticosteroid, and H2-histamine antagonist prior to each infusion
   • Monitor for capillary leak syndrome (potentially life-threatening)
3. Intensive chemotherapy regimens 1, 3
   • Acute leukemia (AL)-like regimens
   • Hyper-CVAD-based therapy (has shown high CR rates of 80%)

For Patients Who Achieve Complete Remission:

• Proceed to hematopoietic cell transplantation (HCT) 1, 3, 4
  • Allogeneic HCT preferred (shows superior outcomes)
  • Autologous HCT if allogeneic not feasible
  • Studies suggest being in first remission during HCT significantly enhances median overall survival 1

For Patients Not Eligible for Intensive Therapy:

For patients with low performance status, poor nutritional status (serum albumin <3.2 g/dL), or those who cannot tolerate intensive therapy:

• For localized lung lesions: Focal radiation therapy 1
• For systemic disease: 1
  • Venetoclax-based regimens (BCL2 is overexpressed in majority of BPDCN patients)
  • Systemic steroids
  • Supportive care

For Relapsed/Refractory Disease:

1. Evaluate for CNS disease and administer intrathecal chemotherapy prophylaxis 1
2. Treatment options: 1
   • Clinical trial (preferred)
   • Tagraxofusp-erzs (if not previously used)
   • Chemotherapy (if not previously given)
   • Local radiation to isolated lung lesions
   • Venetoclax-based regimens
   • Systemic steroids

Monitoring and Follow-up

• Monitor CBC including platelets every 1-3 months for first 2 years, then every 3-6 months for up to 5 years 1
• For patients with prior evidence of extramedullary disease (including lung), repeat PET/CT scan is recommended 1
• Bone marrow evaluation only if cytopenias develop or if peripheral smear is abnormal 1

Important Considerations

• Prognosis: Median overall survival is poor (8-12 months) with conventional chemotherapy alone 1, 4
• Multidisciplinary approach: Decisions about management should involve consultation at a high-volume center, and referral to an academic institution should be considered 1
• Donor search: For eligible patients, a donor search should be initiated early, especially at first relapse 1
• Palliative care integration: Early palliative care should be considered alongside disease-directed therapy to improve quality of life and symptom management, particularly for dyspnea related to lung involvement 1

Cautions and Pitfalls

• Avoid tagraxofusp-erzs in patients with serum albumin <3.2 g/dL due to increased risk of capillary leak syndrome 1
• Monitor for respiratory complications and pneumonitis, which can be life-threatening 1
• BPDCN can be misdiagnosed due to overlapping features with other hematologic malignancies, particularly when presenting with extramedullary disease 2, 5
• Despite high initial response rates with tagraxofusp-erzs, relapses are common, and outcomes for relapsed/refractory disease remain poor 1

The treatment landscape for BPDCN continues to evolve, with ongoing research into novel targeted therapies. Given the rarity and aggressive nature of this disease, management at centers with expertise in BPDCN is strongly recommended.