Blastic plasmocytoid dendritic cell neoplasm (BPDCN), a rare, highly aggressive haematologic malignancy, often with cutaneous and other extramedullary (e.g., lymph node, viscera) manifestations, is derived from plasmacytoid dendritic cells, which express high levels of CD123.1-3 BPDCN has historically carried a poor prognosis with median overall survival (mOS) ranging from 8–14 months from diagnosis.4 Tagraxofusp is a novel targeted therapy directed to CD123.5 In the largest prospectively designed study in patients with BPDCN to date, the efficacy and safety of tagraxofusp was evaluated in a nonrandomised, single-arm, multicentre study evaluating outcomes in both treatment-naïve and previously-treated patients with BPDCN.
Among the 29 treatment naïve patients treated with tagraxofusp (12 mcg/kg), a 90% overall response rate was demonstrated, in which the majority of responses were complete response (CR), clinical CR (CRc, defined as CR with residual skin abnormality not indicative of active disease). Furthermore, of note, 45% of patients were bridged to stem-cell transplantation, including older patients who might have been excluded from intensive therapy. At the time of the analysis (median follow-up of 25 months), the mOS had yet to be reached. The long-term survival probabilities reached 59% at 18 months and 52% at 24 months. Among the 15 patients with previously treated disease, the overall response rate was 67% (10/15), with meaningful mOS of 8.5 months.
Tagraxofusp has a demonstrated safety profile. The most common adverse reactions in patients with treatment-naïve or previously treated malignancies treated with tagraxofusp at the labelled dose and schedule included: also add decreases in albumin (77%), platelets (65%) and increases in alanine (82%) and aspartate (79%) aminotransferase levels. On the basis of this dataset, tagraxofusp is FDA-approved for treatment of adult and paediatric patients,6,7 aged 2 years and older, with BPDCN, and is commercially available in the USA. Tagraxofusp is the first and only approved treatment for BPDCN and the first approved CD123-targeted therapy. Tagraxofusp is additionally being clinically evaluated in other indications including chronic myelomonocytic leukaemia, myelofibrosis, acute myeloid leukaemia, and multiple myeloma.