The Future of CD123 Targeting in BPCDN Treatment

As the blastic plasmacytoid dendritic cell neoplasm (BPDCN) landscape matures, new agents are entering the pipeline to address the limitations of first-generation therapies. In this episode, Andrew A. Lane, MD, PhD, Dana-Farber Cancer Institute, offers an overview of pivekimab sunirine and CD123-directed antibody-drug conjugates (ADCs) in the BPDCN pipeline.

In the phase 1/2 CADENZA trial (NCT03386513), treatment with pivekimab sunirine produced a complete response (CR) and CR with minimal skin abnormality (CRc) rate of 75% (95% CI, 50.9%-91.3%) and an overall response rate (ORR) of 80% (95% CI, 56.3%-94.3%) among patients with frontline de novo BPDCN (n = 20). The respective rates were 70% (95% CI, 51.3%-84.4%) and 85% (95% CI, 68.1%-94.9%) for all patients in the frontline setting (n = 33) as well as 14% (95% CI, 5.7%-26.3%) and 35% (95% CI, 22.4%-49.9%) for those with relapsed/refractory disease (n = 51).

Other agents in development include chimeric antigen receptor (CAR) T-cell therapies and bispecific T-cell engagers (BiTEs) targeting CD123. Lane acknowledged that these treatment regimens may represent the next wave of cellular precision medicine. HE added that the diversification of the BPDCN toolkit ensures that therapy can be increasingly tailored to the individual’s fitness level and logistical needs.