Tagraxofusp: CD123-Targeted Therapy for Frontline Treatment of BPDCN
An expert discusses how treatment selection in blastic plasmacytoid dendritic cell neoplasm (BPDCN) involves balancing disease-specific targeting and patient fitness, with tagraxofusp remaining the frontline standard due to its efficacy and favorable hematologic recovery, whereas venetoclax/azacitidine may be reserved for less fit patients or relapsed settings.
Summary for Physicians: Treatment Selection Considerations in BPDCN
TAG vs Acute Myeloid Leukemia (AML)–Like Regimens (eg, Venetoclax/Azacitidine):
- TAG (Tagraxofusp): Preferred front line for BPDCN due to disease-specific targeting (CD123) and proven efficacy in both skin and marrow involvement.
- Best suited for patients with preserved organ function and manageable comorbidities.
- Requires close monitoring for capillary leak syndrome (CLS) and liver toxicity.
- Venetoclax/Azacitidine: Considered in patients ineligible for TAG due to comorbidities, prior CLS, or in relapsed/refractory settings.
- Broader myeloid activity but lacks CD123 specificity.
- May be favored in cases with overlapping AML features or in combination trials.
Treatment Adaptation Based on Recent Evidence (Konopleva et al, ASH 2024):
- Updated data from the pivotal trial showed favorable hematologic recovery parameters with TAG, including:
- Rapid blast reduction
- Improved platelet and neutrophil counts over time
- Lower early mortality compared with historical AML regimens
- These findings reinforce TAG’s frontline role and support its use even in older or cytopenic patients when monitored appropriately.
Takeaway: Treatment selection hinges on balancing disease biology, patient fitness, and risk of adverse events. TAG remains the standard for frontline BPDCN treatment, with evolving data continuing to shape its application and integration with central nervous system–directed therapy.
