Durable outcomes with manageable safety leading to prolonged survival with tagraxofusp for treatment-naïve patients with blastic plasmacytoid dendritic cell neoplasm: real world results from a European Named Patient Program.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive, poor-prognostic, and CD123-overexpressing orphan hematologic malignancy for which tagraxofusp, a CD123-targeted fusion protein, is the only approved drug. In this retrospective study, safety and efficacy of tagraxofusp were assessed through real-world clinical practice data, collected in patients with BPDCN who received tagraxofusp via a European Named Patient Program (2019-2024). Twenty-six adults with treatment-naïve BPDCN received 12 µg/kg tagraxofusp intravenously daily on days 1-5 (or by day 10) of a 21-day cycle. Primary endpoints were complete response (CR) rates and incidence/severity of capillary leak syndrome (CLS). Secondary endpoints included hematopoietic stem cell transplantation (HSCT), overall survival (OS), and safety. At a median follow-up of 13.5 months, the overall response rate (ORR) was 90% (65% CR); the median duration of response (DOR) was 10.3 months. In 12 evaluable patients who were bridged to HSCT, the pre-transplant ORR was 92% (75% CR), with 14.7 months median DOR. Median OS was 20.2 months (95% CI 10.2-not estimable) in the overall population and 37.0 months (95% CI 10.7-not estimable) in patients bridged to HSCT. CLS events were diagnosed in 13 patients (50%); 68% occurred in cycle 1; 54% were grade 2, and 46% grade 3/4. Treatment-related non-hematologic grade 3/4 adverse events (AEs) or serious AEs were reported in 12 patients (46%); 9 patients (35%) had treatment-related grade 3/4 hematologic AEs. These real-world findings showed no new safety signals and confirmed that tagraxofusp is the first-line treatment of choice for most patients with BPDCN.