Novel Agents Improving Outcomes for Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm

Sangeetha Venugopal, MD, MS, provides an overview of how patients with blastic plasmacytoid dendritic cell neoplasms (BPDCN) are diagnosed.

Andrew Lane, MD, PhD, explains that blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare blood cancer that usually presents with red to purple skin lesions and requires an expert hematopathologist to diagnose using specific immunohistochemistry markers. He notes that central nervous system involvement is more common than previously thought, so all BPDCN patients should get lumbar punctures and intrathecal chemotherapy. The treatment goal is remission followed by allogeneic stem cell transplant for possible long-term remission or cure, as no therapies alone have proven sufficient. The only FDA-approved drug is tagraxofusp, though intensive ALL-like chemotherapy remains standard.

Sangeetha Venugopal, MD, MS, discusses pivekimab sunirine (PVEK), a novel CD123-targeting antibody-drug conjugate for blastic plasmacytoid dendritic cell neoplasm (BPDCN). PVEK showed promising response rates in treatment-naïve BPDCN patients in an early trial and was reasonably well-tolerated without concerning safety signals. Its FDA breakthrough therapy designation in relapsed/refractory BPDCN was based on phase 1 data suggesting good efficacy even after tagraxofusp (TAG). Early trials also support PVEK's potential in CD123+ acute myeloid leukemia, both as monotherapy and when combined with other agents like azacitidine and venetoclax.

Phyu Aung, MD, PhD, FCAP, a dermatopathologist, discusses key challenges in diagnosing and treating blastic plasmacytoid dendritic cell neoplasm (BPDCN). Definitive diagnosis is difficult given BPDCN’s heterogeneous features and frequent skin and CNS involvement. Recent advances have utilized immunophenotyping and targeted CD123, which is overexpressed on BPDCN cells. However, resistance develops with CD123 monotherapy. She notes that while testing aids BPDCN insights, more prognostic markers are needed, and emphasizes that continued cross-disciplinary research is critical to better outcomes.

Dr. Andrew Lane discusses CD123-targeted therapies, particularly the antibody-drug conjugate pivekimab sunirine (PVEK), for treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN). He notes PVEK's promising response rates and safety profile from early trial data, including lower risk of concerning side effects like capillary leak syndrome that can occur with the currently approved CD123-targeting agent tagraxofusp. In closing, he emphasizes accurately diagnosing BPDCN via expert hematopathology review and referral to specialized centers taking a cross-disciplinary approach, as combining emerging CD123-directed therapies with stem cell transplant as appropriate gives the best chance for optimal BPDCN management.