AML-465 Tagraxofusp, an Anti-CD123 Therapy, in Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm: Sub-Analysis of a Pivotal Trial by Age and Baseline Disease Involvement

Context: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive myeloid malignancy characterized by plasmacytoid dendritic cells that aberrantly express IL-3 receptor alpha (CD123). Tagraxofusp (TAG), a first-in-class CD123-targeted therapy, is the only approved treatment for BPDCN. In the pivotal trial TAG demonstrated a 57% complete response (CR) or clinical CR (CRc) and 75% objective response rate (ORR) in first-line patients. Objective: To determine CR+CRc, ORR, survival, and safety by age and baseline disease site involvement (skin-only, systemic-only, and skin+systemic). Design: Sub-analysis of a 4-stage, single-arm phase 1/2 trial (NCT02113982) Setting: Eight US institutions Patients: 65 BPDCN patients receiving first-line therapy. Interventions: TAG 12 mcg/kg on days 1–5 of a 21-day cycle. Main Outcome Measures: Response criteria for BPDCN and CTCAE criteria. Results: CR/CRc and ORR were similar among age groups: <60y (n=17): 59% and 77%; >/=60-</=75y (n=39): 59% and 74%; and?>75y (n=9): 44% and 78%, respectively. Patients with skin+systemic baseline disease (65%) had CR/CRc and ORRs of 50% and 76%, respectively. Twenty-one patients were bridged to hematopoietic stem cell transplantation (HSCT); 58% had baseline disease in ≥2 sites, with probability of survival at 12 and 24 months of 81% and 69%, respectively. In 44 patients not transplanted, four had prolonged responses >6 months; probability of survival at 12 and 24 months was 42% and 24%, respectively. Most common treatment-emergent adverse events (TEAEs) across all age cohorts were increased ALT (67%) and increased AST (61%). Most common TEAEs in the skin-only group were increased ALT and pyrexia (53% each); increased ALT, increased AST, fatigue, and nausea (75% each) in systemic-only group; increased ALT (71%) and increased AST (64%) in the skin+systemic group. Thirteen patients experienced capillary leak syndrome (3 grade 3, 1 grade 4, 2 grade 5). Conclusions: TAG as a first-line treatment for BPDCN was efficacious across all cohorts including older and patients with significant baseline disease. High rates of durable CRs enabled over half of patients in CR to be bridged to HSCT. Safety events were manageable and similar for older vs younger patients. Baseline disease involvement did not appear to predispose patients to different TEAEs.