Unique Therapy for a Rare Blood Cancer

Blastic plasmacytoid dendritic-cell neoplasm (BPDCN) is a rare, highly aggressive malignancy that responds poorly to conventional therapy with intensive acute leukemia or lymphoma chemotherapy regimens.

Given that virtually all cases of BPDCN express the interleukin-3 (IL-3) receptor alpha (CD123), investigators conducted an industry-supported, multicenter, open-label study in which tagraxofusp — a CD123-directed fusion cytotoxin linking IL-3 with truncated diphtheria toxin — was administered to 47 patients with BPDCN (median age, 70 years; 32 were previously untreated). Patients received daily infusions of tagraxofusp (7 or 12 µg/kg) on days 1 to 5 of each 21-day cycle until disease progression or unacceptable toxicity.

At a median follow-up of 19 months (range, 1 to 42 months), of the 29 untreated patients who received the 12 µg/kg dose of tagraxofusp, 90% responded and 72% achieved complete remission (the primary outcome); almost half of responding patients proceeded to allogeneic hematopoietic stem cell transplantation (HCT; 10 patients) or autologous HCT (3 patients). The 24-month overall survival (OS) for responding patients was 52%. Of the 15 patients with relapse or disease progression after prior treatment, 67% responded and 1 patient proceeded to allogeneic HCT; median OS was 8.5 months. Toxicities included elevated liver enzymes, hypoalbuminemia, edema, and thrombocytopenia. Capillary leak syndrome occurred in 18% of patients, resulting in 2 deaths.