AML-373: Tagraxofusp, a CD123-Targeted Therapy, in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Results of a Landmark Clinical Trial

Abstract

Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, hematologic malignancy, comprised of clonal plasmacytoid dendritic cells that are CD123-positive and associated with historically poor outcomes. In 2018, tagraxofusp (TAG), a targeted therapy directed to CD123, became the first-in-class FDA approved treatment for children and adults with BPDCN ages 2 years and older. Treatment with TAG resulted in durable clinical responses with a manageable safety profile in both treatment-naive and relapsed/refractory (R/R) patients. Herein, we present long-term follow-up results ( NCT02113982 ). Objectives To assess the safety and efficacy of TAG in patients with untreated and previously treated BPDCN. Methods In this multicenter, multi-stage, single-arm trial 44 patients with treatment-naive or R/R BPDCN were treated at the indicated dose (12 mcg/kg). In Stage 1 (dose escalation) patients received TAG daily IV infusions at 7 or 12 mcg/kg on days 1–5 of a 21-day cycle. In Stage 2 (expansion) and Stage 3 (pivotal, confirmatory), TAG was dosed at 12 mcg/kg. Key efficacy measures included objective response rate (ORR), complete response (CR), clinical CR (CRc), defined as CR with residual skin abnormality not indicative of active disease, and overall survival (OS). Results Twenty-nine treatment-naive and 15 R/R BPDCN patients were treated for a median duration of 5 and 3 cycles, respectively. Most common treatment emergent adverse events (TEAEs) include hypoalbuminemia, increased transaminases, thrombocytopenia, nausea, fatigue and pyrexia. The most serious adverse event was capillary leak syndrome (CLS), 19% in all grades (one patient with Grade 4 and two with Grade 5). Incidence of TEAEs leading to TAG discontinuation was 2%; temporary dose interruptions for TEAE management were common (68%). In treatment-naive patients ORR was 90%, CR+CRc rate was 72%, and 45% were bridged to stem cell transplant. Median time to response was rapid; 65% of patients achieved complete response by C2. Median overall survival was 26 months; 24-month survival probabilities of 52%. In R/R patients, ORR was 67%, including 2 CR+CRc. Conclusions In the largest prospectively designed study conducted to date, TAG demonstrated robust and durable responses with a median OS of 26 months and a well-characterized safety profile including recognition for CLS.